Signal transduction

1438: 1722:). An analysis of multiple V region sequences by Wu and Kabat identified locations within the V region that were hypervariable and which, they hypothesized, combined in the folded protein to form the antigen recognition site. Thus, within a relatively short time a plausible model was developed for the molecular basis of immunological specificity, and for mediation of biological function through the Fc domain. Crystallization of an IgG molecule soon followed ) confirming the inferences based on sequencing, and providing an understanding of immunological specificity at the highest level of resolution. 1430: 127: 1562: 851: 146: 6299: 1069:. All hormones that act by regulation of gene expression have two consequences in their mechanism of action; their effects are produced after a characteristically long period of time and their effects persist for another long period of time, even after their concentration has been reduced to zero, due to a relatively slow turnover of most enzymes and proteins that would either deactivate or terminate ligand binding onto the receptor. 111:, and so on. Depending on the efficiency of the nodes, a signal can be amplified (a concept known as signal gain), so that one signaling molecule can generate a response involving hundreds to millions of molecules. As with other signals, the transduction of biological signals is characterised by delay, noise, signal feedback and feedforward and interference, which can range from negligible to pathological. With the advent of 704:, the latter permitting the release of second messenger molecules. The total strength of signal amplification by a GPCR is determined by the lifetimes of the ligand-receptor complex and receptor-effector protein complex and the deactivation time of the activated receptor and effectors through intrinsic enzymatic activity; e.g. via protein kinase phosphorylation or b-arrestin-dependent internalization. 874:. Ligand binding to the extracellular domain of integrins changes the protein's conformation, clustering it at the cell membrane to initiate signal transduction. Integrins lack kinase activity; hence, integrin-mediated signal transduction is achieved through a variety of intracellular protein kinases and adaptor molecules, the main coordinator being 1753:

is used. The latter observation was consistent with earlier findings by Fanger et al. These observations tied a biological response to events and structural details of molecules on the cell surface. A preponderance of evidence soon developed that receptor dimerization initiates responses (reviewed in

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and Perelson who found the size distribution of clusters as a function of time, and its dependence on the affinity and valence of the ligand. Subsequent theories for basophils and mast cells were developed by Goldstein and Sobotka and their collaborators, all aimed at the analysis of dose-response

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Gene activations and metabolism alterations are examples of cellular responses to extracellular stimulation that require signal transduction. Gene activation leads to further cellular effects, since the products of responding genes include instigators of activation; transcription factors produced as

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In plants, there are no bona fide integrin receptors identified to date; nevertheless, several integrin-like proteins were proposed based on structural homology with the metazoan receptors. Plants contain integrin-linked kinases that are very similar in their primary structure with the animal ILKs.

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Signal transduction by a GPCR begins with an inactive G protein coupled to the receptor; the G protein exists as a heterotrimer consisting of Gα, Gβ, and Gγ subunits. Once the GPCR recognizes a ligand, the conformation of the receptor changes to activate the G protein, causing Gα to bind a molecule

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of the inside part of the receptor, a process sometimes called "receptor activation". This results in either the activation of an enzyme domain of the receptor or the exposure of a binding site for other intracellular signaling proteins within the cell, eventually propagating the signal through the

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and allow the passage of only calcium to move through. This causes the cytosolic concentration of Calcium to increase, causing a cascade of intracellular changes and activity. In addition, calcium and DAG together works to activate PKC, which goes on to phosphorylate other molecules,

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ensues. Such requirements for extracellular stimulation are necessary for controlling cell behavior in unicellular and multicellular organisms; signal transduction pathways are perceived to be so central to biological processes that a large number of diseases are attributed to their dysregulation.

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Such observations led to a number of theoretical (mathematical) developments. The first of these was a simple model proposed by Bell which resolved an apparent paradox: clustering forms stable networks; i.e. binding is essentially irreversible, whereas the affinities of antibodies secreted by B

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are structurally distinct from other protein kinases and are found in prokaryotes, fungi, and plants as part of a two-component signal transduction mechanism: a phosphate group from ATP is first added to a histidine residue within the kinase, then transferred to an aspartate residue on a receiver

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has on its surface immunoglobulin receptors whose antigen-binding site is identical to that of antibodies that are secreted by the cell when it encounters an antigen, and more specifically a particular B cell clone secretes antibodies with identical sequences. The final piece of the story, the

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and the extracellular medium) is critical for homeostasis. There are three ways in which cells can detect osmotic stimuli: as changes in macromolecular crowding, ionic strength, and changes in the properties of the plasma membrane or cytoskeleton (the latter being a form of mechanotransduction).

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Ligand binding to cell surface receptors is also critical to motility, a phenomenon that is best understood in single-celled organisms. An example is a detection and response to concentration gradients by bacteria -–the classic mathematical theory appearing in. A recent account can be found in

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and a ligand-binding domain; the zinc fingers stabilize DNA binding by holding its phosphate backbone. DNA sequences that match the receptor are usually hexameric repeats of any kind; the sequences are similar but their orientation and distance differentiate them. The ligand-binding domain is

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An example of an ion allowed into the cell during a ligand-gated ion channel opening is Ca; it acts as a second messenger initiating signal transduction cascades and altering the physiology of the responding cell. This results in amplification of the synapse response between synaptic cells by

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of the cell, with one part of the receptor on the outside of the cell and the other on the inside. Signal transduction occurs as a result of a ligand binding to the outside region of the receptor (the ligand does not pass through the membrane). Ligand-receptor binding induces a change in the

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First messengers are the signaling molecules (hormones, neurotransmitters, and paracrine/autocrine agents) that reach the cell from the extracellular fluid and bind to their specific receptors. Second messengers are the substances that enter the cytoplasm and act within the cell to trigger a

1695:—were published on the subject. The term first appeared in a paper's title in 1979. Widespread use of the term has been traced to a 1980 review article by Rodbell: Research papers focusing on signal transduction first appeared in large numbers in the late 1980s and early 1990s. 1706:

The purpose of this section is to briefly describe some developments in immunology in the 1960s and 1970s, relevant to the initial stages of transmembrane signal transduction, and how they impacted our understanding of immunology, and ultimately of other areas of cell biology.

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of GTP and dissociate from the other two G-protein subunits. The dissociation exposes sites on the subunits that can interact with other molecules. The activated G protein subunits detach from the receptor and initiate signaling from many downstream effector proteins such as

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The majority of signal transduction pathways involve the binding of signaling molecules, known as ligands, to receptors that trigger events inside the cell. The binding of a signaling molecule with a receptor causes a change in the conformation of the receptor, known as

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a result of a signal transduction cascade can activate even more genes. Hence, an initial stimulus can trigger the expression of a large number of genes, leading to physiological events like the increased uptake of glucose from the blood stream and the migration of

1303:, which when activated produces another second messenger, cGMP. NO can also act through covalent modification of proteins or their metal co-factors; some have a redox mechanism and are reversible. It is toxic in high concentrations and causes damage during 1247:

that releases more calcium upon binding with it. The nature of calcium in the cytosol means that it is active for only a very short time, meaning its free state concentration is very low and is mostly bound to organelle molecules like

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For example, steroids act directly as transcription factor (gives slow response, as transcription factor must bind DNA, which needs to be transcribed. Produced mRNA needs to be translated, and the produced protein/peptide can undergo

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A ligand-gated ion channel, upon binding with a ligand, changes conformation to open a channel in the cell membrane through which ions relaying signals can pass. An example of this mechanism is found in the receiving cell of a neural

927:, has been shown to be a critical element in the plant immune response to signal molecules from bacterial pathogens and plant sensitivity to salt and osmotic stress. ILK1 protein interacts with the high-affinity potassium transporter 1107:

enabling its passage into the nucleus is accessible. Steroid receptors, on the other hand, may be repressive on gene expression when their transactivation domain is hidden. Receptor activity can be enhanced by phosphorylation of

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Bago R, Sommer E, Castel P, Crafter C, Bailey FP, Shpiro N, Baselga J, Cross D, Eyers PA, Alessi DR (2016) The hVps34-SGK3 pathway alleviates sustained PI3K/Akt inhibition by stimulating mTORC1 and tumour growth. EMBO Journal

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When signaling pathways interact with one another they form networks, which allow cellular responses to be coordinated, often by combinatorial signaling events. At the molecular level, such responses include changes in the

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Kagey-Sobotka, A, Dembo, M, Goldstein, B, Metzger, H and Lichtenstein, L M (1981) Qualitative characteristics of histamine release from human basophils by covalently cross-linked IgE. The Journal of Immunology 127 (6),

913:. Epithelial cells (which are non-circulating) normally have active integrins at their cell membrane, helping maintain their stable adhesion to underlying stromal cells that provide signals to maintain normal functioning. 601:

that facilitate signaling protein interactions and coordination of signaling complexes necessary to respond to a particular stimulus. Enzymes and adaptor proteins are both responsive to various second messenger molecules.

1749:(IgE) functions as a surface receptor – degranulate, depends on the concentration of anti IgE antibodies to which they are exposed, and results in a redistribution of surface molecules, which is absent when monovalent 1718:. Biochemical experiments revealed that these so-called Bence Jones proteins consisted of 2 discrete domains –one that varied from one molecule to the next (the V domain) and one that did not (the Fc domain or the 290:

when overexpressed or mutated. This leads to constitutive activation of the pathway, which may or may not be overturned by compensation mechanisms. In the case of HER2, which acts as a dimerization partner of other

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Wilson CH, Ali ES, Scrimgeour N, Martin AM, Hua J, Tallis GA, et al. (March 2015). "Steatosis inhibits liver cell store-operated Ca²⁺ entry and reduces ER Ca²⁺ through a protein kinase C-dependent mechanism".

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Fanger, M W, Hart, D A, Wells, J V, and Nisonoff, A J (1970) Requirement for cross-linkage in the stimulation of transformation of rabbit peripheral lymphocytes by antiglobulin reagents J. Immun., 105, 1484 -

651:. With nearly 800 members, this is the largest family of membrane proteins and receptors in mammals. Counting all animal species, they add up to over 5000. Mammalian GPCRs are classified into 5 major families: 812:

groups linked to their carboxyl ends. Upon activation, they assign proteins to specific membrane subdomains where they participate in signaling. Activated RTKs in turn activate small G proteins that activate

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The basis for signal transduction is the transformation of a certain stimulus into a biochemical signal. The nature of such stimuli can vary widely, ranging from extracellular cues, such as the presence of

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Dembo, M and Goldstein, B (1978) Theory of equilibrium binding of symmetric bivalent haptens to cell surface antibody: application to histamine release from basophils. The Journal of Immunology 121 (1),

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Wu, T T, Kabat, E A (1970) An analysis of the sequences of the variable regions of Bence Jones proteins and myeloma light chains and their implications for antibody complementarity. J. Exp. Med. 132:

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and derivatives of vitamins A and D. To initiate signal transduction, the ligand must pass through the plasma membrane by passive diffusion. On binding with the receptor, the ligands pass through the

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When activated, toll-like receptors (TLRs) take adapter molecules within the cytoplasm of cells in order to propagate a signal. Four adaptor molecules are known to be involved in signaling, which are

821:. Once activated, these exchange factors can activate more small G proteins, thus amplifying the receptor's initial signal. The mutation of certain RTK genes, as with that of GPCRs, can result in the 782:

are important for signal transduction, either acting downstream of , or as membrane-embedded or cell-soluble versions in their own right. The process of signal transduction involves around 560 known

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Yamamoto M, Sato S, Hemmi H, Uematsu S, Hoshino K, Kaisho T, et al. (November 2003). "TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway".

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to survive. This requirement has led to the development of complex mechanotransduction pathways, allowing cells to sense the stiffness of the substratum. Such signaling is mainly orchestrated in

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Lipophilic second messenger molecules are derived from lipids residing in cellular membranes; enzymes stimulated by activated receptors activate the lipids by modifying them. Examples include

5885: 1134:. These receptors are located in the nucleus and are not accompanied by HSPs. They repress their gene by binding to their specific DNA sequence when no ligand binds to them, and vice versa. 1675:, which strongly influenced the cell's metabolism. Thus, he deduced that the G-protein is a transducer that accepts glucagon molecules and affects the cell. For this, he shared the 1994 4556:

Sarma, V R, Silverton, E W, Davies, D R, Terry W D (1971) The three-dimensional structure at 6 A resolution of a human gamma G1 immunoglobulin molecule, J Biol. Chem. 246 (11) 3752- 9

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or suppression of genes that cause certain responses. Thousands of genes are activated by TLR signaling, implying that this method constitutes an important gateway for gene modulation.

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Yamamoto M, Sato S, Hemmi H, Sanjo H, Uematsu S, Kaisho T, et al. (November 2002). "Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4".

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Following are some major signaling pathways, demonstrating how ligands binding to their receptors can affect second messengers and eventually result in altered cellular responses.

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Kirsten Jung, Florian Fabiani, Elisabeth Hoyer, and Jürgen Lassak 2018 Bacterial transmembrane signaling systems and their engineering for biosensing Open Biol. Apr; 8(4): 180023

1259:. The three main pathways that lead to its activation are GPCR pathways, RTK pathways, and gated ion channels; it regulates proteins either directly or by binding to an enzyme. 796:

As is the case with GPCRs, proteins that bind GTP play a major role in signal transduction from the activated RTK into the cell. In this case, the G proteins are members of the

1683:. Thus, the characterization of RTKs and GPCRs led to the formulation of the concept of "signal transduction", a word first used in 1972. Some early articles used the terms 766:

residues within the intracellular kinase domains of the RTKs, causing conformational changes. Subsequent to this, the receptors' kinase domains are activated, initiating

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How does T cell receptor clustering impact signal transduction? Jesse Goyette, Daniel J. Nieves, Yuanqing Ma, Katharina Gaus Journal of Cell Science 2019 132:jcs226423

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Sobotka, A.K. Dembo, M, Goldstein, B and Lichtenstein, L M, (1979) Antigen-specific desensitization of human basophils The Journal of Immunology, 122 (2) 511-517

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Burnet, F M (1976) A modification of Jerne's theory of antibody production using the concept of clonal selection. CA: A Cancer Journal for Clinicians 26 (2) 119–21

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are another subset of nuclear receptors. They can be activated by an endocrine-synthesized ligand that entered the cell by diffusion, a ligand synthesised from a

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response. In essence, second messengers serve as chemical relays from the plasma membrane to the cytoplasm, thus carrying out intracellular signal transduction.

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are maintained in an inactive state to avoid epithelial cell attachment; they are activated only in response to stimuli such as those received at the site of an

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G protein–coupled receptors (GPCRs) are a family of integral transmembrane proteins that possess seven transmembrane domains and are linked to a heterotrimeric

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Becker, K E, Ishizaka, T, Metzger, H, Ishizaka, K and Grimley, P M (1973) Surface IgE on Human Basophils during histamine release. J Exp med, 138, 394-408

3028:"Point mutation causing constitutive signaling of CXCR2 leads to transforming activity similar to Kaposi's sarcoma herpesvirus-G protein-coupled receptor" 1091:

are a subclass of nuclear receptors located primarily within the cytosol. In the absence of steroids, they associate in an aporeceptor complex containing

526: 5759: 1004:, such as those that travel along nerves, by depolarizing the membrane of post-synaptic cells, resulting in the opening of voltage-gated ion channels. 978: 723:

of CXCR2 in an active conformation despite the absence of chemokine-binding. This meant that chemokine receptors can contribute to cancer development.

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region of the genes activated by the hormone-receptor complex. Due to their enabling gene transcription, they are alternatively called inductors of

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Papin JA, Hunter T, Palsson BO, Subramaniam S (February 2005). "Reconstruction of cellular signalling networks and analysis of their properties".

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cells increase as the immune response progresses. A theory of the dynamics of cell surface clustering on lymphocyte membranes was developed by

459:, HSF1 then trimerizes, becoming active and upregulating the expression of its target genes. Many other thermosensory mechanisms exist in both 4666:

MacNab, R., and D. E. Koshland, Jr. (1972). The gradient-sensing mechanism in bacterial chemotaxis. Proc. Natl. Acad. Sci. U.S.A. 69:2509-2512

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Koboldt DC, Fulton RS, McLellan MD, Schmidt H, Kalicki-Veizer J, McMichael JF, et al. (The Cancer Genome Atlas Network) (October 2012).

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Klemm J D, Schreiber S L, Crabtree G R (1998) Ann. Rev. Immunol. Dimerization as a regulatory mechanism in signal transduction 16: 569-592

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of the plasma membrane provided all the ingredients for a new model for the initiation of signal transduction; viz, receptor dimerization.

1034:, are soluble proteins localized within their respective areas. The typical ligands for nuclear receptors are non-polar hormones like the 72:

and conformational changes in proteins, as well as changes in their location. These molecular events are the basic mechanisms controlling

48:, although in some cases the term sensor is used. The changes elicited by ligand binding (or signal sensing) in a receptor give rise to a 1957:

Kolch W, Halasz M, Granovskaya M, Kholodenko BN (September 2015). "The dynamic control of signal transduction networks in cancer cells".

177:. Many other intercellular signal relay mechanisms exist in multicellular organisms, such as those that govern embryonic development. 5355: 4910: 1487: 3510:"Differential binding of calmodulin-related proteins to their targets revealed through high-density Arabidopsis protein microarrays" 3337:

Hehlgans S, Haase M, Cordes N (January 2007). "Signalling via integrins: implications for cell survival and anticancer strategies".

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Reiterer V, Eyers PA, Farhan H (September 2014). "Day of the dead: pseudokinases and pseudophosphatases in physiology and disease".

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Dupont S, Morsut L, Aragona M, Enzo E, Giulitti S, Cordenonsi M, et al. (June 2011). "Role of YAP/TAZ in mechanotransduction".

1403:(EGFR), which causes dimerization and autophosphorylation of the EGFR, which in turn activates the intracellular signaling pathway . 5862: 5498: 5406: 5303: 5017: 4973: 4831: 87:

Each component (or node) of a signaling pathway is classified according to the role it plays with respect to the initial stimulus.

4772: 5820: 5675: 5216: 4806: 3461:"The Raf-like Kinase ILK1 and the High Affinity K+ Transporter HAK5 Are Required for Innate Immunity and Abiotic Stress Response" 2701:

Shamovsky I, Ivannikov M, Kandel ES, Gershon D, Nudler E (March 2006). "RNA-mediated response to heat shock in mammalian cells".

1589:, were responsible for the release of "internal secretions" with physiological effects. Bernard's "secretions" were later named " 758:; the dimer is stabilized by ligands binding to the receptor. The interaction between the cytoplasmic domains stimulates the auto 597:, the latter controlling the release of intracellular calcium stores into the cytoplasm. Other activated proteins interact with 403:

These changes are detected by proteins known as osmosensors or osmoreceptors. In humans, the best characterised osmosensors are

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Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S (December 2002). "The protein kinase complement of the human genome".

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cells, most intracellular proteins activated by a ligand/receptor interaction possess an enzymatic activity; examples include

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can also mediate mechanotransduction. Specialised forms of mechanotransduction within the nervous system are responsible for

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Sako Y, Minoghchi S, Yanagida T (March 2000). "Single-molecule imaging of EGFR signalling on the surface of living cells".

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In addition to nitric oxide, other electronically activated species are also signal-transducing agents in a process called

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patterns of immune cells and their biological correlates. For a recent review of clustering in immunological systems see.

429:. Additionally, animal cells contain a conserved mechanism to prevent high temperatures from causing cellular damage, the 6164: 4314:

Rensing L (1972). "Periodic geophysical and biological signals as Zeitgeber and exogenous inducers in animal organisms".

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The combination of these signals is integrated into altered cytoplasmic machinery which leads to altered cell behaviour.

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Not all classifications of signaling molecules take into account the molecular nature of each class member. For example,

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belong to a wide range of molecular classes, as do neurotransmitters, which range in size from small molecules such as

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Cowan WM (March 2001). "Viktor Hamburger and Rita Levi-Montalcini: the path to the discovery of nerve growth factor".

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Missale C, Nash SR, Robinson SW, Jaber M, Caron MG (January 1998). "Dopamine receptors: from structure to function".

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Important differences exist between integrin-signaling in circulating blood cells and non-circulating cells such as

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Tonndorf J (September 1975). "Davis-1961 revisited. Signal transmission in the cochlear hair cell-nerve junction".

1400: 878:. As shown in the adjacent picture, cooperative integrin-RTK signaling determines the timing of cellular survival, 81: 2856:

Fredriksson R, Schiöth HB (May 2005). "The repertoire of G-protein-coupled receptors in fully sequenced genomes".

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Calcium is used in many processes including muscle contraction, neurotransmitter release from nerve endings, and

660: 69: 5810: 5012: 4988: 4968: 3409:"Arabidopsis NDR1 is an integrin-like protein with a role in fluid loss and plasma membrane-cell wall adhesion" 1719: 1552:

leading to altered cellular activity. End-effects include taste, manic depression, tumor promotion, etc.

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Rodbell M (March 1980). "The role of hormone receptors and GTP-regulatory proteins in membrane transduction".

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Integrins are produced by a wide variety of cells; they play a role in cell attachment to other cells and the

5569: 5022: 1483: 4713: 897:; integrins of circulating cells are normally inactive. For example, cell membrane integrins on circulating 6319: 6159: 5903: 5775: 5750: 5741: 5603: 5256: 1209: 1138: 4758: 1360:

to sites of infection. The set of genes and their activation order to certain stimuli is referred to as a

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signaling cascades of downstream cytoplasmic molecules that facilitate various cellular processes such as

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The first hints of this were obtained by Becker et al who demonstrated that the extent to which human

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A Cell Based Immunocytochemical Assay For Monitoring Kinase Signaling Pathways And Drug Efficacy (PDF)

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of signaling pathways and networks has become an essential tool to understand cellular functions and

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DeLisi, C and Perelson A (1976). The kinetics of aggregation phenomena, J. theor. Biol. 62, 159-210

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results in its binding to signaling proteins that are then activated; it is then sequestered in the

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Certain intracellular receptors of the immune system are cytoplasmic receptors; recently identified

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brought to the cell through the bloodstream or a completely intracellularly synthesised ligand like

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residues at their N-terminal as a result of another signal transduction pathway, a process called

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in 1962, led to more detailed insights into the molecular basis of cell signaling, in particular

1621: 1461: 1396: 1186: 345: 155: 61: 4836: 3080:"Role of receptor tyrosine kinase transmembrane domains in cell signaling and human pathologies" 6106: 6079: 4938: 4732: 4466:"Lipid synthesis: an indicator of antigen-induced signal transduction in antigen-binding cells" 1668: 1633: 1479: 1344: 1119: 1021: 875: 605:

Many adaptor proteins and enzymes activated as part of signal transduction possess specialized

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Bell, G I (1974) Model for the binding of multivalent antigens to cells, Nature Lond. 248, 430

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Schlessinger J (November 1988). "Signal transduction by allosteric receptor oligomerization".

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Signal Transduction - The Virtual Library of Biochemistry, Molecular Biology and Cell Biology

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that can diffuse through the plasma membrane and affect nearby cells. It is synthesised from

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This article is about signaling at the cellular level. For systemic signal transduction, see

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Delbridge LM, O'Riordan MX (February 2007). "Innate recognition of intracellular bacteria".

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and many other processes. In multicellular organisms, signal transduction pathways regulate

6203: 6199: 6151: 5134: 4272: 3905: 3676: 3580: 3521: 3171: 2710: 2473: 2328: 2281: 2156: 2100:

Beato M, Chávez S, Truss M (April 1996). "Transcriptional regulation by steroid hormones".

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domain on a different protein or the kinase itself, thus activating the aspartate residue.

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of receptors that exist in a constitutively activated state; such mutated genes may act as

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that bind to specific secondary messenger molecules. For example, calcium ions bind to the

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The sensing of temperature in cells is known as thermoception and is primarily mediated by

213: 123:, including signaling rewiring mechanisms underlying responses to acquired drug resistance. 4374:"The effect of N-acylglucosamines on the biosynthesis and secretion of insulin in the rat" 1561: 1433:

How to read signal transduction diagrams, what does normal arrow and flathead arrow means.

675:, with a few GPCR groups being difficult to classify due to low sequence similarity, e.g. 165:

attrition. Traditionally, signals that reach the central nervous system are classified as

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Popescu SC, Popescu GV, Bachan S, Zhang Z, Seay M, Gerstein M, et al. (March 2007).

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is the process by which a chemical or physical signal is transmitted through a cell as a

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Literature-curated human signaling network, the largest human signaling network database

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Cascade of intracellular and molecular events for transmission/amplification of signals

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Berg, H C and Purcell, E M (1977) Physics of chemoreception, Biophys. J 20(2):193-219

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Vogelstein B, Kinzler KW (August 2004). "Cancer genes and the pathways they control".

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Yamamoto M, Sato S, Hemmi H, Hoshino K, Kaisho T, Sanjo H, et al. (August 2003).

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Brauer EK, Ahsan N, Dale R, Kato N, Coluccio AE, Piñeros MA, et al. (June 2016).

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Mammalian cells require stimulation for cell division and survival; in the absence of

1000:. The influx of ions that occurs in response to the opening of these channels induces 6111: 5007: 4963: 4798: 4537:

Steiner, L A (1996) Immunoglobulin evolution, 30 years on. Glycobiology 6 , 649-656

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Roskoski R (June 2004). "The ErbB/HER receptor protein-tyrosine kinases and cancer".

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Hildebrand E (April 1977). "What does Halobacterium tell us about photoreception?".

4009: 3704: 3653: 3610: 3569:"Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway" 3199: 3061: 3026:

Burger M, Burger JA, Hoch RC, Oades Z, Takamori H, Schraufstatter IU (August 1999).

2450: 2129: 1986: 1725:

The biological significance of these developments was encapsulated in the theory of

1099:(HSPs). The HSPs are necessary to activate the receptor by assisting the protein to 6237: 6208: 6137: 6033: 5966: 4978: 4956: 4952: 4650: 4477: 4430: 4393: 4385: 4346: 4300: 4280: 4237: 4221: 4217: 4180: 4172: 4081: 4044: 4036: 3989: 3952: 3913: 3865: 3826: 3791: 3727: 3684: 3633: 3588: 3539: 3529: 3480: 3472: 3428: 3420: 3381: 3346: 3306: 3296: 3257: 3222: 3179: 3136: 3099: 3091: 3039: 2998: 2988: 2920: 2912: 2885: 2865: 2806: 2765: 2738: 2718: 2673: 2665: 2621: 2617: 2613: 2572: 2531: 2501: 2481: 2428: 2381: 2344: 2336: 2289: 2272:

Goldstein A (September 1976). "Opioid peptides endorphins in pituitary and brain".

2246: 2211: 2174: 2164: 2109: 2072: 2031: 2023: 1966: 1889: 1869: 1781: 1746: 1726: 1715: 1680: 1609:, were discovered in the following years, the mechanisms remained largely unknown. 1449: 1340: 1276: 1216:. Two combined receptor/ion channel proteins control the transport of calcium: the 1088: 1047: 1027: 1009: 832: 583: 391: 373: 357: 233: 104: 4023:

Orton RJ, Sturm OE, Vyshemirsky V, Calder M, Gilbert DR, Kolch W (December 2005).

3957: 3940: 2250: 6116: 5693: 5425: 5420: 5386: 5283: 5035: 4810: 4794: 4776: 4762: 4749: 4708: 4703: 3385: 2770: 2753: 1711: 1598: 1594: 1540: 1508: 1493: 1361: 1336: 1324: 1307:, but is the cause of many other functions like the relaxation of blood vessels, 1100: 1082: 1066: 894: 822: 805: 797: 783: 779: 767: 759: 755: 720: 575: 558: 490: 326: 276: 196:. Most ligands are soluble molecules from the extracellular medium which bind to 116: 4482: 4465: 4025:"Computational modelling of the receptor-tyrosine-kinase-activated MAPK pathway" 3350: 3044: 3027: 866:

and in the transduction of signals from extracellular matrix components such as

582:. Often such enzymes are covalently linked to the receptor. Some of them create 6303: 6249: 6056: 5926: 5397: 3514:

Proceedings of the National Academy of Sciences of the United States of America

3261: 2149:

Proceedings of the National Academy of Sciences of the United States of America

1791: 1692: 1660: 1574: 1457: 1256: 1104: 850: 708: 408: 369: 201: 126: 3731: 3285:"Histidine protein kinases: key signal transducers outside the animal kingdom" 3226: 2834: 2811: 2794: 2754:"Beyond counting photons: trials and trends in vertebrate visual transduction" 2669: 2077: 2060: 411:

of human cells. In yeast, the HOG pathway has been extensively characterised.

6313: 6051: 5415: 5288: 4176: 2993: 2977:"Mechanisms of regulation and function of G-protein-coupled receptor kinases" 2901:"Inactive-state preassembly of G(q)-coupled receptors and G(q) heterotrimers" 1931: 1629: 1586: 1582: 1469: 1453: 1368: 1174: 1131: 1078: 751: 743: 697: 681: 664: 542: 538: 420: 322: 260: 236:

are lipid-soluble and thus cross the plasma membrane to reach cytoplasmic or

5476: 4719: 3917: 3593: 3568: 3534: 3183: 2464:

Kung C (August 2005). "A possible unifying principle for mechanosensation".

2169: 1714:

light chains, which are found in abundance in the urine of individuals with

1573:

The earliest notion of signal transduction can be traced back to 1855, when

854:

An overview of integrin-mediated signal transduction, adapted from Hehlgens

6276: 6041: 6037: 5432: 5270: 4229: 4194: 4093: 4058: 4001: 3966: 3838: 3803: 3739: 3696: 3645: 3602: 3553: 3494: 3442: 3393: 3358: 3320: 3269: 3234: 3191: 3113: 3053: 3012: 2934: 2877: 2869: 2820: 2779: 2730: 2687: 2635: 2586: 2577: 2560: 2545: 2536: 2519: 2493: 2442: 2393: 2358: 2293: 2223: 2202:

Ronnett GV, Moon C (2002). "G proteins and olfactory signal transduction".

2188: 2086: 2045: 2027: 1978: 1881: 1786: 1501: 1468:

components. In many cell types, activation of this pathway promotes

1288: 1249: 1213: 1051: 1043: 1039: 902: 726: 701: 518: 385: 337: 130:

Simplified representation of major signal transduction pathways in mammals.

4323: 4292: 3925: 3879: 3424: 3148: 2433: 2416: 2258: 2121: 6271: 6084: 5335: 4905: 4818: 4491: 4442: 4407: 4358: 2916: 2301: 1357: 1343:. Redox signaling also includes active modulation of electronic flows in 1268: 1073: 883: 867: 579: 460: 268: 217: 73: 3688: 3476: 2722: 2485: 2385: 2340: 6224: 5525: 5320: 4997: 4654: 4434: 4040: 3854:"Signal transduction and gene regulation: the nuclear response to cAMP" 3817:

Forman HJ (November 2009). "Signal transduction and reactive species".

3795: 2012:"Different telomere damage signaling pathways in human and mouse cells" 1700: 1637: 1328: 1142: 910: 898: 775: 672: 614: 587: 522: 514: 464: 395: 264: 221: 77: 4787: 4697:

Netpath - A curated resource of signal transduction pathways in humans

4389: 3095: 145: 6254: 5988: 5847: 5789: 5002: 4920: 4284: 3993: 3372:

Gilcrease MZ (March 2007). "Integrin signaling in epithelial cells".

2417:"Cellular mechanotransduction: putting all the pieces together again" 1742: 1672: 1649: 1645: 1372: 1308: 1236: 1031: 906: 905:. In a similar manner, integrins at the cell membrane of circulating 879: 826: 809: 712: 648: 571: 510: 506: 318: 225: 205: 4742: 1970: 1873: 1452:: A pathway that couples intracellular responses to the binding of 958: 6298: 6046: 4085: 2520:"Osmosensory mechanisms in cellular and systemic volume regulation" 1664: 1602: 1590: 1312: 1292: 1272: 1233: 1170: 1081:

of nucleic receptors prior to binding and providing structures for

1057:

Activated nuclear receptors attach to the DNA at receptor-specific

871: 845: 763: 668: 353: 349: 330: 256: 252: 162: 3637: 1158: 808:. They act as molecular switches usually tethered to membranes by 267:. Moreover, some molecules may fit into more than one class, e.g. 44:. Proteins responsible for detecting stimuli are generally termed 6028: 5867: 5591: 5437: 4866: 1606: 1566: 1548: 1524: 1465: 1205: 1166: 1127: 1035: 997: 747: 610: 399: 361: 158:, to intracellular events, such as the DNA damage resulting from 120: 4782: 4463: 1956: 1691:. In 2007, a total of 48,377 scientific papers—including 11,211 961:. These adapters activate other intracellular molecules such as 103:. Such effectors are typically proteins and are often linked to 5872: 5660: 5655: 5365: 4464:

Kenny JJ, Martínez-Maza O, Fehniger T, Ashman RF (April 1979).

2700: 1759: 1750: 1730: 1578: 1473: 1304: 1109: 791: 739: 735: 502: 296: 170: 4755: 5886:

deficiencies of intracellular signaling peptides and proteins

5670: 5665: 5627: 5612: 5579: 5574: 5535: 5530: 5518: 5513: 5508: 5503: 5491: 5469: 5464: 5459: 5236: 5231: 5226: 5221: 5181: 5176: 5114: 5109: 5104: 5099: 5074: 5069: 5064: 5059: 5054: 5049: 5044: 1859: 1671:

disassociated glucagon from this receptor and stimulated the

1486:) (see picture), and, thus, further effects depend mainly on 1482:: In humans, cAMP works by activating protein kinase A (PKA, 1287:

Nitric oxide (NO) acts as a second messenger because it is a

1162: 1154: 966: 962: 950: 946: 482: 453: 449: 445: 441: 365: 334: 166: 2314: 5852: 5837: 5622: 5562: 5557: 5552: 5547: 5486: 5481: 5325: 5298: 5293: 5206: 5201: 5196: 5191: 5186: 5163: 5158: 5153: 5148: 5143: 5094: 5089: 5079: 4814: 4022: 2317:"Comprehensive molecular portraits of human breast tumours" 1150: 954: 928: 818: 434: 341: 292: 283: 229: 4696: 3161: 2061:"Mosaic and regulative development: two faces of one coin" 1149:(LRR) motif similar to TLRs. Some of these molecules like 295:, constitutive activation leads to hyperproliferation and 3780: 3507: 1085:

used for communication with the translational apparatus.

630: 537:

Receptors can be roughly divided into two major classes:

498: 5925: 4765:- Signal transduction pathway mining in PubMed abstracts 4371: 4118:

Alberts B, Lewis J, Raff M, Roberts K, Walter P (2002).

3623: 3566: 2947: 2236: 1839:(2nd ed.). Amsterdam, Netherlands: Academic Press. 1464:. This pathway is very complex and includes many 734:(RTKs) are transmembrane proteins with an intracellular 727:

Tyrosine, Ser/Thr and Histidine-specific protein kinases

4117: 3339:

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

2602:"Osmotic stress signaling and osmoadaptation in yeasts" 2371: 1667:

on a rat's liver cell membrane receptor. He noted that

1644:

to include only signaling from glands, while the terms

149:

3D Medical animation still showing signal transduction.

3717: 3666: 2145:"The further redefining of steroid-mediated signaling" 1072:

Nucleic receptors have DNA-binding domains containing

340:

detects changes and transmits them downstream through

6287: 3979: 3025: 2517: 1656:, while Levi-Montalcini and Cohen shared it in 1986. 625:

and other phosphoinositides do the same thing to the

232:, respectively). In addition, some molecules such as 4512: 4372:

Ashcroft SJ, Crossley JR, Crossley PC (March 1976).

3755: 3283:

Wolanin PM, Thomason PA, Stock JB (September 2002).

3282: 2518:

Pedersen SF, Kapus A, Hoffmann EK (September 2011).

2009: 1698: 1605:

in 1902. Although many other hormones, most notably

750:. To perform signal transduction, RTKs need to form 52:, which is a chain of biochemical events known as a 3458: 3454: 3452: 3336: 3250:

Biochemical and Biophysical Research Communications

3212: 2795:"Phototransduction in ganglion-cell photoreceptors" 1519:). DAG remains bound to the membrane, and IP 977:that amplify the signal, eventually leading to the 527:

intrinsically photosensitive retinal ganglion cells

5760:Sh2 domain-containing protein tyrosine phosphatase 4723:s STKE - Signal Transduction Knowledge Environment 4119: 3896:Rosen OM (September 1987). "After insulin binds". 3851: 2948:Berg JM, Tymoczko JL, Stryer L, Clarke ND (2002). 2855: 1906:Biochemistry of Signal Transduction and Regulation 1754:) in a variety of cell types, including B cells. 1652:began to be used. Sutherland was awarded the 1971 1441:Elements of Signal transduction cascade networking 517:. In the case of the circadian clock, a different 4071: 1710:The relevant events begin with the sequencing of 679:. Other classes exist in eukaryotes, such as the 6311: 3449: 3406: 3120: 2898: 2099: 1565:Occurrence of the term "signal transduction" in 804:, and Raf families, referred to collectively as 4716:- A database about signal transduction pathways 2899:Qin K, Dong C, Wu G, Lambert NA (August 2011). 2651: 1376:Three basic signals determine cellular growth: 3760:(7th ed.). McGraw-Hill. pp. 159–60. 3751: 3749: 3617: 3560: 2751: 2058: 1834: 1224:that transports calcium upon interaction with 738:domain and an extracellular domain that binds 636: 505:. In the case of vision, light is detected by 5911: 4868:Intracellular signaling peptides and proteins 4852: 3938: 3660: 2892: 2565:Journal of the American Society of Nephrology 2524:Journal of the American Society of Nephrology 1929: 1531:then diffuses through the cytosol to bind to 3206: 3155: 3126: 1547:(ER). These channels are specific to 1523:is released as a soluble structure into the 1275:, the former required for the activation of 984: 244:, their stimulation leads to binding to the 4126:(4th ed.). New York: Garland Science. 3810: 3746: 3332: 3330: 2835:"A molecular model for receptor activation" 2647: 2645: 2513: 2511: 2201: 923:, one of the integrin-linked kinase genes, 271:is a neurotransmitter when secreted by the 5918: 5904: 5755:Receptor-like protein tyrosine phosphatase 4859: 4845: 4779:Analytical Biochemistry 338 (2005) 136-142 4513:Gomperts BD, Kramer IM, Tatham PE (2002). 4420: 4414: 4258: 4256: 4113: 4111: 3077: 2606:Microbiology and Molecular Biology Reviews 2010:Smogorzewska A, de Lange T (August 2002). 1577:proposed that ductless glands such as the 1015: 715:receptor CXCR2; mutated cells underwent a 557:and make up most receptors. They span the 548: 493:by activating light-sensitive proteins in 5356:Cyclin-dependent kinase inhibitor protein 4735:at the U.S. National Library of Medicine 4481: 4397: 4184: 4048: 4016: 3956: 3869: 3592: 3543: 3533: 3484: 3432: 3371: 3365: 3310: 3300: 3103: 3073: 3071: 3043: 3002: 2992: 2924: 2810: 2769: 2677: 2625: 2576: 2535: 2432: 2348: 2271: 2265: 2178: 2168: 2076: 2035: 5863:Phosphatidylethanolamine binding protein 5499:Interleukin-1 receptor associated kinase 4911:Ca2+/calmodulin-dependent protein kinase 4506: 4365: 4336: 4330: 3932: 3891: 3889: 3756:Vander AJ, Sherman J, Luciano D (1998). 3407:Knepper C, Savory EA, Day B (May 2011). 3327: 3247: 3241: 2851: 2849: 2847: 2752:Burns ME, Arshavsky VY (November 2005). 2642: 2558: 2508: 2216:10.1146/annurev.physiol.64.082701.102219 1560: 1436: 1428: 1145:cells and interact with ligands using a 849: 711:was inserted into the gene encoding the 525:, is responsible for detecting light in 144: 125: 4316:International Journal of Biometeorology 4313: 4307: 4262: 4253: 4145: 4143: 4108: 2974: 2599: 2230: 2195: 1923: 1490:, which vary based on the type of cell. 1141:(NLRs) reside in the cytoplasm of some 629:of proteins such as the kinase protein 14: 6312: 5618:Focal adhesion protein-tyrosine kinase 4901:Intracellular calcium-sensing proteins 3852:Lalli E, Sassone-Corsi P (July 1994). 3816: 3068: 3019: 2792: 2561:"How does the brain sense osmolality?" 2414: 2142: 2136: 1902: 1862:Nature Reviews. Molecular Cell Biology 1640:in 1956, prompted the redefinition of 1476:are associated with aberrations in it. 1169:and initiate processing of particular 934: 5899: 4840: 4457: 4423:Biophysics of Structure and Mechanism 4207: 3895: 3886: 3845: 2844: 2745: 1835:Bradshaw RA, Dennis EA, eds. (2010). 1677:Nobel Prize in Physiology or Medicine 1654:Nobel Prize in Physiology or Medicine 1505:phosphatidylinositol 4,5-bisphosphate 1411:Permissive (cell-matrix interactions) 1350: 1200:The release of calcium ions from the 427:transient receptor potential channels 405:transient receptor potential channels 4351:10.1001/archotol.1975.00780380006002 4244: 4158: 4140: 3973: 2652:Sengupta P, Garrity P (April 2013). 2463: 2093: 2059:Lawrence PA, Levine M (April 2006). 1936:. San Francisco: Benjamin Cummings. 1180: 909:are normally kept inactive to avoid 778:. Many Ser/Thr and dual-specificity 302: 6165:Transcription preinitiation complex 3858:The Journal of Biological Chemistry 3831:10.1016/j.freeradbiomed.2009.09.002 3819:Free Radical Biology & Medicine 1262: 815:guanine nucleotide exchange factors 617:, allowing it to bind and activate 321:means that most cell types require 275:and a hormone when secreted by the 24: 6133:Signal transducing adaptor protein 5843:Signal transducing adaptor protein 5018:3',5'-cyclic-GMP phosphodiesterase 4974:3',5'-cyclic-AMP phosphodiesterase 4250:Bradshaw & Dennis (2010) p. 2. 4149:Bradshaw & Dennis (2010) p. 1. 1393:Transcription independent response 1318: 931:and with the calcium sensor CML9. 833:Histidine-specific protein kinases 25: 6346: 5838:Activating transcription factor 6 5252:G protein-coupled receptor kinase 4804:Cell cycle - Homo sapiens (human) 4690: 3939:Massagué J, Gomis RR (May 2006). 1418: 1026:Intracellular receptors, such as 690:fungal mating pheromone receptors 390:Cellular and systemic control of 224:can also bind to such receptors ( 6297: 5382:Phosphoinositide phospholipase C 3941:"The logic of TGFbeta signaling" 3302:10.1186/gb-2002-3-10-reviews3013 1401:epidermal growth factor receptor 1383:Transcription dependent response 1299:and works through activation of 1061:(HRE) sequences, located in the 917:In the experimental model plant 4678: 4669: 4660: 4643: 4633: 4624: 4614: 4605: 4596: 4587: 4577: 4568: 4559: 4550: 4540: 4531: 4201: 4161:"One hundred years of hormones" 4152: 4065: 3774: 3711: 3501: 3400: 3276: 2968: 2954:. San Francisco: W.H. Freeman. 2941: 2827: 2786: 2694: 2593: 2552: 2457: 2408: 2365: 2308: 1817:Two-component regulatory system 1282: 1228:on its cytosolic side; and the 1161:signaling, whereas others like 555:integral transmembrane proteins 5821:GTP-binding protein regulators 5811:GTP-binding protein regulators 4752:, from Nature Publishing Group 4222:10.1146/annurev.neuro.24.1.551 3129:Trends in Biochemical Sciences 2618:10.1128/MMBR.66.2.300-372.2002 2052: 2003: 1993: 1950: 1896: 1853: 1828: 1720:Fragment crystallizable region 1408:Inhibitory (cell-cell contact) 1388:posttranslational modification 707:A study was conducted where a 414: 173:to neuron in a process called 13: 1: 5570:Rho-associated protein kinase 4743:UCSD-Nature Signaling Gateway 4210:Annual Review of Neuroscience 4122:Molecular biology of the cell 3958:10.1016/j.febslet.2006.04.033 3871:10.1016/S0021-9258(17)32442-0 3720:Current Opinion in Immunology 3078:Li E, Hristova K (May 2006). 2559:Verbalis JG (December 2007). 2251:10.1152/physrev.1998.78.1.189 1822: 1488:cAMP-dependent protein kinase 1484:cAMP-dependent protein kinase 1380:Stimulatory (growth factors) 1077:additionally responsible for 379: 288:ligand-independent activation 248:of steroid-responsive genes. 169:. These are transmitted from 5776:Dual-specificity phosphatase 5751:protein tyrosine phosphatase 5257:AMP-activated protein kinase 4823:Pathway Interaction Database 3386:10.1016/j.canlet.2006.03.031 3141:10.1016/0968-0004(88)90219-8 2771:10.1016/j.neuron.2005.10.014 2114:10.1016/0039-128X(96)00030-X 1930:Reece J, Campbell N (2002). 1632:. Their work, together with 1210:smooth endoplasmic reticulum 1054:, altering gene expression. 839: 553:Extracellular receptors are 532: 7: 5800:apoptosis signaling pathway 4483:10.4049/jimmunol.122.4.1278 3351:10.1016/j.bbcan.2006.09.001 3045:10.4049/jimmunol.163.4.2017 2204:Annual Review of Physiology 1812:Protein–protein interaction 1770: 1513:inositol 1,4,5-triphosphate 1425:List of signalling pathways 1347:biological macromolecules. 1165:interact with inflammatory 637:G protein–coupled receptors 627:Pleckstrin homology domains 619:calmodulin-dependent kinase 84:in a wide variety of ways. 10: 6351: 4788:Signaling PAthway Database 4657:Published 11 February 2019 4339:Archives of Otolaryngology 3262:10.1016/j.bbrc.2004.04.150 1837:Handbook of Cell Signaling 1601:, Starling had discovered 1569:-indexed papers since 1977 1556: 1422: 1195: 1184: 1059:hormone-responsive element 1019: 988: 938: 843: 643:G protein–coupled receptor 640: 474: 418: 383: 306: 184: 180: 138: 134: 95:, while receptors are the 42:series of molecular events 29: 6217: 6187: 6150: 6125: 6102: 6093: 6065: 6019: 6012: 5937: 5881: 5830: 5809: 5788: 5768: 5740: 5721: 5711: 5686: 5644:Serine/threonine/tyrosine 5643: 5602: 5405: 5395: 5374: 5348: 5269: 5247: 5130: 5031: 4987: 4937: 4928: 4919: 4893: 4874: 3732:10.1016/j.coi.2006.11.005 3227:10.1016/j.tcb.2014.03.008 2812:10.1007/s00424-007-0242-2 2793:Berson DM (August 2007). 2670:10.1016/j.cub.2013.03.009 2078:10.1016/j.cub.2006.03.016 1909:. Wiley-VCH. p. 15. 1012:involved in the synapse. 985:Ligand-gated ion channels 732:Receptor tyrosine kinases 242:steroid hormone receptors 32:Transduction (physiology) 6245:Neuroendocrine signaling 5858:Olfactory marker protein 5445:Glycogen synthase kinase 4948:Heterotrimeric G protein 4737:Medical Subject Headings 4177:10.1038/sj.embor.7400444 2994:10.3748/wjg.v12.i48.7753 2143:Hammes SR (March 2003). 1663:examined the effects of 1301:soluble guanylyl cyclase 991:Ligand-gated ion channel 717:malignant transformation 477:Visual phototransduction 470: 5651:Dual-specificity kinase 5361:Cyclin-dependent kinase 4378:The Biochemical Journal 4029:The Biochemical Journal 3918:10.1126/science.2442814 3784:The Biochemical Journal 3594:10.1126/science.1087262 3535:10.1073/pnas.0611615104 3184:10.1126/science.1075762 2905:Nature Chemical Biology 2600:Hohmann S (June 2002). 2170:10.1073/pnas.0530224100 1797:Gene regulatory network 1699:Signal transduction in 1622:epidermal growth factor 1597:in 1905. Together with 1397:epidermal growth factor 1187:Second messenger system 1120:Retinoic acid receptors 1103:in a way such that the 1016:Intracellular receptors 790:, encoded by the human 549:Extracellular receptors 346:cell adhesion molecules 282:Some receptors such as 6107:cAMP-dependent pathway 4783:www.Redoxsignaling.com 3215:Trends in Cell Biology 2975:Yang W, Xia S (2006). 2870:10.1124/mol.104.009001 2858:Molecular Pharmacology 2578:10.1681/ASN.2007070825 2537:10.1681/ASN.2010121284 2415:Ingber DE (May 2006). 2294:10.1126/science.959823 1959:Nature Reviews. Cancer 1669:guanosine triphosphate 1634:Earl Wilbur Sutherland 1570: 1480:cAMP-dependent pathway 1442: 1434: 1243:receptor but having a 1022:Intracellular receptor 876:integrin-linked kinase 859: 746:receptors such as the 661:metabotropic glutamate 485:controls the sense of 273:central nervous system 198:cell surface receptors 150: 131: 99:, which then activate 6233:Synaptic transmission 6229:Neurocrine signaling 6152:Transcription factors 5999:PI3K/AKT/mTOR pathway 5732:Protein phosphatase 2 5543:p21-activated kinases 4768:Huaxian Chen, et al. 4470:Journal of Immunology 4159:Tata JR (June 2005). 3425:10.1104/pp.110.169656 3032:Journal of Immunology 2981:World J Gastroenterol 2654:"Sensing temperature" 2434:10.1096/fj.05-5424rev 2239:Physiological Reviews 1564: 1545:endoplasmic reticulum 1440: 1432: 1423:Further information: 1239:, similar to the InsP 1226:inositol triphosphate 1202:endoplasmic reticulum 1032:cytoplasmic receptors 903:inflammatory response 853: 677:vomeronasal receptors 452:. With help from the 187:Ligand (biochemistry) 175:synaptic transmission 148: 141:Stimulus (physiology) 129: 113:computational biology 107:, which can activate 5135:G beta-gamma complex 4729:, published by AAAS. 4318:. 16 Suppl: 113–25. 2917:10.1038/nchembio.642 2028:10.1093/emboj/cdf433 1745:—for which bivalent 1689:sensory transduction 1618:Rita Levi-Montalcini 1472:, and many forms of 920:Arabidopsis thaliana 864:extracellular matrix 772:cell differentiation 686:cyclic AMP receptors 437:from complexes with 344:. Calcium-dependent 329:, regions where the 214:extracellular matrix 212:. Components of the 6320:Signal transduction 6262:Mechanotransduction 6250:Exocrine signalling 6057:Signaling molecules 5931:Signal transduction 5714:protein phosphatase 5587:Ribosomal s6 kinase 4733:Signal+Transduction 4725:, from the journal 4515:Signal transduction 4277:1980Natur.284...17R 3982:Nature Cell Biology 3910:1987Sci...237.1452R 3689:10.1038/nature01182 3681:2002Natur.420..324Y 3585:2003Sci...301..640Y 3526:2007PNAS..104.4730P 3477:10.1104/pp.16.00035 3295:(10): REVIEWS3013. 3176:2002Sci...298.1912M 2723:10.1038/nature04518 2715:2006Natur.440..556S 2486:10.1038/nature03896 2478:2005Natur.436..647K 2386:10.1038/nature10137 2341:10.1038/nature11412 2333:2012Natur.490...61T 2286:1976Sci...193.1081G 2161:2003PNAS..100.2168H 1802:Hormonal imprinting 1729:which holds that a 1685:signal transmission 1642:endocrine signaling 1614:nerve growth factor 1327:. Examples include 1147:leucine-rich repeat 935:Toll-like receptors 742:; examples include 495:photoreceptor cells 439:heat shock proteins 431:heat-shock response 394:(the difference in 309:Mechanotransduction 194:receptor activation 109:secondary effectors 50:biochemical cascade 38:Signal transduction 6272:Ion channel gating 6004:Integrin receptors 5938:Signaling pathways 4884:MAP kinase pathway 4809:2012-10-23 at the 4793:2012-09-17 at the 4775:2012-02-22 at the 4761:2019-05-11 at the 4748:2013-02-12 at the 4702:2012-09-20 at the 4655:10.1242/jcs.226423 4517:. Academic Press. 4435:10.1007/BF00536457 4041:10.1042/BJ20050908 3796:10.1042/bj20140881 1736:Fluid mosaic model 1571: 1500:: PLC cleaves the 1443: 1435: 1351:Cellular responses 1295:and oxygen by the 1245:feedback mechanism 1230:ryanodine receptor 1139:NOD-like receptors 1097:heatshock proteins 941:Toll-like receptor 860: 317:in the tissues of 315:basement membranes 313:The prevalence of 151: 132: 97:signal transducers 82:cell communication 70:post-translational 6285: 6284: 6267:Phototransduction 6225:Intracrine action 6183: 6182: 6146: 6145: 6034:Neurotransmitters 5893: 5892: 5848:I-kappa B protein 5784: 5783: 5707: 5706: 5344: 5343: 5265: 5264: 5008:Guanylate cyclase 4964:Adenylate cyclase 4799:Kyushu University 4524:978-0-12-289631-6 4390:10.1042/bj1540701 4133:978-0-8153-3218-3 3767:978-0-07-067065-5 3626:Nature Immunology 3170:(5600): 1912–34. 3096:10.1021/bi060609y 2961:978-0-7167-4954-7 1943:978-0-8053-6624-2 1903:Krauss G (2008). 1807:Metabolic pathway 1612:The discovery of 1507:(PIP2), yielding 1333:hydrogen peroxide 1181:Second messengers 1089:Steroid receptors 1028:nuclear receptors 1002:action potentials 584:second messengers 303:Mechanical forces 240:. In the case of 238:nuclear receptors 210:neurotransmitters 105:second messengers 101:primary effectors 76:, proliferation, 54:signaling pathway 18:Signal transducer 16:(Redirected from 6342: 6302: 6301: 6293: 6238:Chemical synapse 6138:Scaffold protein 6100: 6099: 6095:Second messenger 6021:Receptor ligands 6017: 6016: 5920: 5913: 5906: 5897: 5896: 5723:Serine/threonine 5719: 5718: 5407:Serine/threonine 5403: 5402: 5023:Protein kinase G 4979:Protein kinase A 4935: 4934: 4926: 4925: 4861: 4854: 4847: 4838: 4837: 4685: 4682: 4676: 4673: 4667: 4664: 4658: 4647: 4641: 4637: 4631: 4628: 4622: 4618: 4612: 4609: 4603: 4600: 4594: 4591: 4585: 4581: 4575: 4572: 4566: 4563: 4557: 4554: 4548: 4544: 4538: 4535: 4529: 4528: 4510: 4504: 4503: 4485: 4461: 4455: 4454: 4418: 4412: 4411: 4401: 4369: 4363: 4362: 4334: 4328: 4327: 4311: 4305: 4304: 4285:10.1038/284017a0 4260: 4251: 4248: 4242: 4241: 4205: 4199: 4198: 4188: 4156: 4150: 4147: 4138: 4137: 4125: 4115: 4106: 4105: 4069: 4063: 4062: 4052: 4035:(Pt 2): 249–61. 4020: 4014: 4013: 3994:10.1038/35004044 3977: 3971: 3970: 3960: 3936: 3930: 3929: 3904:(4821): 1452–8. 3893: 3884: 3883: 3873: 3864:(26): 17359–62. 3849: 3843: 3842: 3814: 3808: 3807: 3778: 3772: 3771: 3758:Human Physiology 3753: 3744: 3743: 3715: 3709: 3708: 3664: 3658: 3657: 3621: 3615: 3614: 3596: 3564: 3558: 3557: 3547: 3537: 3505: 3499: 3498: 3488: 3465:Plant Physiology 3456: 3447: 3446: 3436: 3413:Plant Physiology 3404: 3398: 3397: 3369: 3363: 3362: 3334: 3325: 3324: 3314: 3304: 3280: 3274: 3273: 3245: 3239: 3238: 3210: 3204: 3203: 3159: 3153: 3152: 3124: 3118: 3117: 3107: 3075: 3066: 3065: 3047: 3023: 3017: 3016: 3006: 2996: 2972: 2966: 2965: 2945: 2939: 2938: 2928: 2896: 2890: 2889: 2853: 2842: 2841: 2839: 2831: 2825: 2824: 2814: 2790: 2784: 2783: 2773: 2749: 2743: 2742: 2709:(7083): 556–60. 2698: 2692: 2691: 2681: 2649: 2640: 2639: 2629: 2597: 2591: 2590: 2580: 2556: 2550: 2549: 2539: 2515: 2506: 2505: 2472:(7051): 647–54. 2461: 2455: 2454: 2436: 2412: 2406: 2405: 2380:(7350): 179–83. 2369: 2363: 2362: 2352: 2312: 2306: 2305: 2280:(4258): 1081–6. 2269: 2263: 2262: 2234: 2228: 2227: 2199: 2193: 2192: 2182: 2172: 2140: 2134: 2133: 2097: 2091: 2090: 2080: 2056: 2050: 2049: 2039: 2016:The EMBO Journal 2007: 2001: 1997: 1991: 1990: 1954: 1948: 1947: 1927: 1921: 1920: 1900: 1894: 1893: 1857: 1851: 1850: 1832: 1782:Scaffold protein 1747:Immunoglobulin E 1727:clonal selection 1716:multiple myeloma 1681:Alfred G. Gilman 1636:'s discovery of 1541:calcium channels 1450:MAPK/ERK pathway 1399:(EGF) binds the 1341:hydrogen sulfide 1277:protein kinase C 1263:Lipid messengers 1232:named after the 1048:nuclear membrane 1010:dendritic spines 1008:remodelling the 895:epithelial cells 806:small G proteins 748:insulin receptor 599:adaptor proteins 392:osmotic pressure 358:mechanosensation 234:steroid hormones 200:. These include 93:first messengers 21: 6350: 6349: 6345: 6344: 6343: 6341: 6340: 6339: 6310: 6309: 6308: 6296: 6288: 6286: 6281: 6213: 6179: 6142: 6121: 6117:Lipid signaling 6089: 6061: 6008: 5933: 5924: 5894: 5889: 5877: 5826: 5805: 5780: 5764: 5736: 5703: 5694:Arginine kinase 5682: 5639: 5598: 5391: 5387:Phospholipase C 5370: 5340: 5261: 5243: 5173: 5140: 5126: 5041: 5036:G alpha subunit 5027: 4983: 4915: 4889: 4870: 4865: 4811:Wayback Machine 4795:Wayback Machine 4777:Wayback Machine 4763:Wayback Machine 4750:Wayback Machine 4704:Wayback Machine 4693: 4688: 4683: 4679: 4674: 4670: 4665: 4661: 4648: 4644: 4638: 4634: 4629: 4625: 4619: 4615: 4610: 4606: 4601: 4597: 4592: 4588: 4582: 4578: 4573: 4569: 4564: 4560: 4555: 4551: 4545: 4541: 4536: 4532: 4525: 4511: 4507: 4462: 4458: 4419: 4415: 4370: 4366: 4335: 4331: 4312: 4308: 4271:(5751): 17–22. 4261: 4254: 4249: 4245: 4206: 4202: 4157: 4153: 4148: 4141: 4134: 4116: 4109: 4074:Nature Medicine 4070: 4066: 4021: 4017: 3978: 3974: 3951:(12): 2811–20. 3937: 3933: 3894: 3887: 3850: 3846: 3815: 3811: 3779: 3775: 3768: 3754: 3747: 3716: 3712: 3675:(6913): 324–9. 3665: 3661: 3632:(11): 1144–50. 3622: 3618: 3579:(5633): 640–3. 3565: 3561: 3506: 3502: 3457: 3450: 3405: 3401: 3370: 3366: 3335: 3328: 3281: 3277: 3246: 3242: 3211: 3207: 3160: 3156: 3125: 3121: 3090:(20): 6241–51. 3076: 3069: 3024: 3020: 2973: 2969: 2962: 2946: 2942: 2897: 2893: 2854: 2845: 2837: 2833: 2832: 2828: 2799:Pflügers Archiv 2791: 2787: 2750: 2746: 2699: 2695: 2658:Current Biology 2650: 2643: 2598: 2594: 2557: 2553: 2516: 2509: 2462: 2458: 2413: 2409: 2370: 2366: 2327:(7418): 61–70. 2313: 2309: 2270: 2266: 2235: 2231: 2200: 2196: 2141: 2137: 2098: 2094: 2065:Current Biology 2057: 2053: 2022:(16): 4338–48. 2008: 2004: 1998: 1994: 1971:10.1038/nrc3983 1955: 1951: 1944: 1928: 1924: 1917: 1901: 1897: 1874:10.1038/nrm1570 1858: 1854: 1847: 1833: 1829: 1825: 1777:Adaptor protein 1773: 1712:myeloma protein 1704: 1599:William Bayliss 1595:Ernest Starling 1559: 1536: 1530: 1522: 1518: 1509:diacyl glycerol 1497: 1427: 1421: 1394: 1384: 1362:genetic program 1353: 1337:carbon monoxide 1325:redox signaling 1321: 1319:Redox signaling 1285: 1265: 1252:when inactive. 1242: 1221: 1198: 1189: 1183: 1157:that activates 1105:signal sequence 1083:transactivation 1067:gene expression 1024: 1018: 993: 987: 943: 937: 888:differentiation 848: 842: 784:protein kinases 780:protein kinases 768:phosphorylation 760:phosphorylation 756:plasma membrane 729: 645: 639: 624: 607:protein domains 595: 576:tyrosine kinase 559:plasma membrane 551: 535: 491:circadian clock 479: 473: 423: 417: 407:present in the 388: 382: 327:focal adhesions 311: 305: 286:are capable of 277:adrenal medulla 246:promoter region 189: 183: 143: 137: 35: 28: 23: 22: 15: 12: 11: 5: 6348: 6338: 6337: 6335:Neurochemistry 6332: 6330:Cell signaling 6327: 6322: 6307: 6306: 6283: 6282: 6280: 6279: 6274: 6269: 6264: 6259: 6258: 6257: 6247: 6242: 6241: 6240: 6235: 6227: 6221: 6219: 6218:Other concepts 6215: 6214: 6212: 6211: 6206: 6197: 6191: 6189: 6185: 6184: 6181: 6180: 6178: 6177: 6172: 6167: 6162: 6156: 6154: 6148: 6147: 6144: 6143: 6141: 6140: 6135: 6129: 6127: 6123: 6122: 6120: 6119: 6114: 6109: 6103: 6097: 6091: 6090: 6088: 6087: 6082: 6077: 6071: 6069: 6063: 6062: 6060: 6059: 6054: 6052:Growth factors 6049: 6044: 6031: 6025: 6023: 6014: 6010: 6009: 6007: 6006: 6001: 5996: 5991: 5986: 5981: 5976: 5971: 5970: 5969: 5964: 5954: 5949: 5947: 5941: 5939: 5935: 5934: 5927:Cell signaling 5923: 5922: 5915: 5908: 5900: 5891: 5890: 5882: 5879: 5878: 5876: 5875: 5870: 5865: 5860: 5855: 5850: 5845: 5840: 5834: 5832: 5828: 5827: 5825: 5824: 5815: 5813: 5807: 5806: 5804: 5803: 5794: 5792: 5786: 5785: 5782: 5781: 5779: 5778: 5772: 5770: 5766: 5765: 5763: 5762: 5757: 5747: 5745: 5738: 5737: 5735: 5734: 5728: 5726: 5716: 5709: 5708: 5705: 5704: 5702: 5701: 5696: 5690: 5688: 5684: 5683: 5681: 5680: 5679: 5678: 5673: 5668: 5663: 5658: 5647: 5645: 5641: 5640: 5638: 5637: 5632: 5631: 5630: 5625: 5615: 5609: 5607: 5600: 5599: 5597: 5596: 5595: 5594: 5584: 5583: 5582: 5577: 5567: 5566: 5565: 5560: 5555: 5550: 5540: 5539: 5538: 5533: 5523: 5522: 5521: 5516: 5511: 5506: 5496: 5495: 5494: 5489: 5484: 5474: 5473: 5472: 5467: 5462: 5457: 5452: 5442: 5441: 5440: 5430: 5429: 5428: 5423: 5412: 5410: 5400: 5398:protein kinase 5393: 5392: 5390: 5389: 5384: 5378: 5376: 5372: 5371: 5369: 5368: 5363: 5358: 5352: 5350: 5346: 5345: 5342: 5341: 5339: 5338: 5333: 5328: 5323: 5318: 5313: 5308: 5307: 5306: 5301: 5296: 5286: 5281: 5275: 5273: 5267: 5266: 5263: 5262: 5260: 5259: 5254: 5248: 5245: 5244: 5242: 5241: 5240: 5239: 5234: 5229: 5224: 5219: 5214: 5209: 5204: 5199: 5194: 5189: 5184: 5179: 5171: 5168: 5167: 5166: 5161: 5156: 5151: 5146: 5138: 5131: 5128: 5127: 5125: 5124: 5123: 5122: 5117: 5112: 5107: 5102: 5097: 5092: 5087: 5082: 5077: 5072: 5067: 5062: 5057: 5052: 5047: 5039: 5032: 5029: 5028: 5026: 5025: 5020: 5015: 5010: 5005: 5000: 4994: 4992: 4985: 4984: 4982: 4981: 4976: 4971: 4966: 4961: 4960: 4959: 4944: 4942: 4932: 4930:Heterotrimeric 4923: 4917: 4916: 4914: 4913: 4908: 4903: 4897: 4895: 4891: 4890: 4888: 4887: 4878: 4876: 4872: 4871: 4864: 4863: 4856: 4849: 4841: 4835: 4834: 4829: 4820: 4801: 4785: 4780: 4766: 4753: 4740: 4730: 4717: 4711: 4706: 4692: 4691:External links 4689: 4687: 4686: 4677: 4668: 4659: 4642: 4632: 4623: 4613: 4604: 4595: 4586: 4576: 4567: 4558: 4549: 4539: 4530: 4523: 4505: 4476:(4): 1278–84. 4456: 4413: 4364: 4329: 4306: 4252: 4243: 4216:(1): 551–600. 4200: 4151: 4139: 4132: 4107: 4086:10.1038/nm1087 4064: 4015: 3972: 3931: 3885: 3844: 3809: 3773: 3766: 3745: 3710: 3659: 3616: 3559: 3520:(11): 4730–5. 3500: 3471:(2): 1470–84. 3448: 3419:(1): 286–300. 3399: 3374:Cancer Letters 3364: 3326: 3289:Genome Biology 3275: 3240: 3221:(9): 489–505. 3205: 3154: 3119: 3067: 3038:(4): 2017–22. 3018: 2987:(48): 7753–7. 2967: 2960: 2940: 2891: 2864:(5): 1414–25. 2843: 2826: 2785: 2764:(3): 387–401. 2744: 2693: 2641: 2592: 2571:(12): 3056–9. 2551: 2530:(9): 1587–97. 2507: 2456: 2407: 2364: 2307: 2264: 2245:(1): 189–225. 2229: 2210:(1): 189–222. 2194: 2155:(5): 2168–70. 2135: 2092: 2051: 2002: 1992: 1949: 1942: 1922: 1916:978-3527313976 1915: 1895: 1852: 1845: 1826: 1824: 1821: 1820: 1819: 1814: 1809: 1804: 1799: 1794: 1792:Cell signaling 1789: 1784: 1779: 1772: 1769: 1703: 1697: 1661:Martin Rodbell 1630:growth factors 1587:adrenal glands 1575:Claude Bernard 1558: 1555: 1554: 1553: 1534: 1528: 1520: 1516: 1495: 1491: 1477: 1454:growth factors 1420: 1419:Major pathways 1417: 1413: 1412: 1409: 1406: 1405: 1404: 1391: 1352: 1349: 1345:semiconductive 1320: 1317: 1284: 1281: 1269:diacylglycerol 1264: 1261: 1257:cell migration 1240: 1219: 1197: 1194: 1185:Main article: 1182: 1179: 1153:interact with 1020:Main article: 1017: 1014: 989:Main article: 986: 983: 939:Main article: 936: 933: 844:Main article: 841: 838: 728: 725: 709:point mutation 698:phospholipases 653:rhodopsin-like 641:Main article: 638: 635: 622: 593: 550: 547: 534: 531: 475:Main article: 472: 469: 419:Main article: 416: 413: 409:primary cilium 384:Main article: 381: 378: 370:proprioception 307:Main article: 304: 301: 202:growth factors 185:Main article: 182: 179: 139:Main article: 136: 133: 68:of genes, and 26: 9: 6: 4: 3: 2: 6347: 6336: 6333: 6331: 6328: 6326: 6323: 6321: 6318: 6317: 6315: 6305: 6300: 6295: 6294: 6291: 6278: 6275: 6273: 6270: 6268: 6265: 6263: 6260: 6256: 6253: 6252: 6251: 6248: 6246: 6243: 6239: 6236: 6234: 6231: 6230: 6228: 6226: 6223: 6222: 6220: 6216: 6210: 6207: 6205: 6201: 6198: 6196: 6193: 6192: 6190: 6186: 6176: 6173: 6171: 6168: 6166: 6163: 6161: 6158: 6157: 6155: 6153: 6149: 6139: 6136: 6134: 6131: 6130: 6128: 6124: 6118: 6115: 6113: 6110: 6108: 6105: 6104: 6101: 6098: 6096: 6092: 6086: 6083: 6081: 6080:Intracellular 6078: 6076: 6073: 6072: 6070: 6068: 6064: 6058: 6055: 6053: 6050: 6048: 6045: 6043: 6042:Neurohormones 6039: 6038:Neuropeptides 6035: 6032: 6030: 6027: 6026: 6024: 6022: 6018: 6015: 6011: 6005: 6002: 6000: 5997: 5995: 5992: 5990: 5989:Fas apoptosis 5987: 5985: 5982: 5980: 5977: 5975: 5972: 5968: 5965: 5963: 5960: 5959: 5958: 5955: 5953: 5950: 5948: 5946: 5943: 5942: 5940: 5936: 5932: 5928: 5921: 5916: 5914: 5909: 5907: 5902: 5901: 5898: 5888: 5887: 5880: 5874: 5871: 5869: 5866: 5864: 5861: 5859: 5856: 5854: 5851: 5849: 5846: 5844: 5841: 5839: 5836: 5835: 5833: 5829: 5823: 5822: 5817: 5816: 5814: 5812: 5808: 5802: 5801: 5796: 5795: 5793: 5791: 5787: 5777: 5774: 5773: 5771: 5767: 5761: 5758: 5756: 5752: 5749: 5748: 5746: 5743: 5739: 5733: 5730: 5729: 5727: 5724: 5720: 5717: 5715: 5710: 5700: 5697: 5695: 5692: 5691: 5689: 5685: 5677: 5674: 5672: 5669: 5667: 5664: 5662: 5659: 5657: 5654: 5653: 5652: 5649: 5648: 5646: 5642: 5636: 5633: 5629: 5626: 5624: 5621: 5620: 5619: 5616: 5614: 5611: 5610: 5608: 5605: 5601: 5593: 5590: 5589: 5588: 5585: 5581: 5578: 5576: 5573: 5572: 5571: 5568: 5564: 5561: 5559: 5556: 5554: 5551: 5549: 5546: 5545: 5544: 5541: 5537: 5534: 5532: 5529: 5528: 5527: 5524: 5520: 5517: 5515: 5512: 5510: 5507: 5505: 5502: 5501: 5500: 5497: 5493: 5490: 5488: 5485: 5483: 5480: 5479: 5478: 5475: 5471: 5468: 5466: 5463: 5461: 5458: 5456: 5453: 5451: 5448: 5447: 5446: 5443: 5439: 5436: 5435: 5434: 5431: 5427: 5424: 5422: 5419: 5418: 5417: 5416:Casein kinase 5414: 5413: 5411: 5408: 5404: 5401: 5399: 5394: 5388: 5385: 5383: 5380: 5379: 5377: 5373: 5367: 5364: 5362: 5359: 5357: 5354: 5353: 5351: 5347: 5337: 5334: 5332: 5329: 5327: 5324: 5322: 5319: 5317: 5314: 5312: 5309: 5305: 5302: 5300: 5297: 5295: 5292: 5291: 5290: 5287: 5285: 5282: 5280: 5277: 5276: 5274: 5272: 5268: 5258: 5255: 5253: 5250: 5249: 5246: 5238: 5235: 5233: 5230: 5228: 5225: 5223: 5220: 5218: 5215: 5213: 5210: 5208: 5205: 5203: 5200: 5198: 5195: 5193: 5190: 5188: 5185: 5183: 5180: 5178: 5175: 5174: 5169: 5165: 5162: 5160: 5157: 5155: 5152: 5150: 5147: 5145: 5142: 5141: 5136: 5133: 5132: 5129: 5121: 5118: 5116: 5113: 5111: 5108: 5106: 5103: 5101: 5098: 5096: 5093: 5091: 5088: 5086: 5083: 5081: 5078: 5076: 5073: 5071: 5068: 5066: 5063: 5061: 5058: 5056: 5053: 5051: 5048: 5046: 5043: 5042: 5037: 5034: 5033: 5030: 5024: 5021: 5019: 5016: 5014: 5011: 5009: 5006: 5004: 5001: 4999: 4996: 4995: 4993: 4990: 4986: 4980: 4977: 4975: 4972: 4970: 4967: 4965: 4962: 4958: 4954: 4951: 4950: 4949: 4946: 4945: 4943: 4940: 4936: 4933: 4931: 4927: 4924: 4922: 4918: 4912: 4909: 4907: 4904: 4902: 4899: 4898: 4896: 4892: 4886: 4885: 4880: 4879: 4877: 4873: 4869: 4862: 4857: 4855: 4850: 4848: 4843: 4842: 4839: 4833: 4830: 4828: 4824: 4821: 4819: 4816: 4812: 4808: 4805: 4802: 4800: 4796: 4792: 4789: 4786: 4784: 4781: 4778: 4774: 4771: 4767: 4764: 4760: 4757: 4754: 4751: 4747: 4744: 4741: 4738: 4734: 4731: 4728: 4724: 4722: 4718: 4715: 4712: 4710: 4707: 4705: 4701: 4698: 4695: 4694: 4681: 4672: 4663: 4656: 4652: 4646: 4636: 4627: 4617: 4608: 4599: 4590: 4580: 4571: 4562: 4553: 4543: 4534: 4526: 4520: 4516: 4509: 4501: 4497: 4493: 4489: 4484: 4479: 4475: 4471: 4467: 4460: 4452: 4448: 4444: 4440: 4436: 4432: 4428: 4424: 4417: 4409: 4405: 4400: 4395: 4391: 4387: 4383: 4379: 4375: 4368: 4360: 4356: 4352: 4348: 4345:(9): 528–35. 4344: 4340: 4333: 4325: 4321: 4317: 4310: 4302: 4298: 4294: 4290: 4286: 4282: 4278: 4274: 4270: 4266: 4259: 4257: 4247: 4239: 4235: 4231: 4227: 4223: 4219: 4215: 4211: 4204: 4196: 4192: 4187: 4182: 4178: 4174: 4170: 4166: 4162: 4155: 4146: 4144: 4135: 4129: 4124: 4123: 4114: 4112: 4103: 4099: 4095: 4091: 4087: 4083: 4080:(8): 789–99. 4079: 4075: 4068: 4060: 4056: 4051: 4046: 4042: 4038: 4034: 4030: 4026: 4019: 4011: 4007: 4003: 3999: 3995: 3991: 3988:(3): 168–72. 3987: 3983: 3976: 3968: 3964: 3959: 3954: 3950: 3946: 3942: 3935: 3927: 3923: 3919: 3915: 3911: 3907: 3903: 3899: 3892: 3890: 3881: 3877: 3872: 3867: 3863: 3859: 3855: 3848: 3840: 3836: 3832: 3828: 3825:(9): 1237–8. 3824: 3820: 3813: 3805: 3801: 3797: 3793: 3790:(2): 379–90. 3789: 3785: 3777: 3769: 3763: 3759: 3752: 3750: 3741: 3737: 3733: 3729: 3725: 3721: 3714: 3706: 3702: 3698: 3694: 3690: 3686: 3682: 3678: 3674: 3670: 3663: 3655: 3651: 3647: 3643: 3639: 3638:10.1038/ni986 3635: 3631: 3627: 3620: 3612: 3608: 3604: 3600: 3595: 3590: 3586: 3582: 3578: 3574: 3570: 3563: 3555: 3551: 3546: 3541: 3536: 3531: 3527: 3523: 3519: 3515: 3511: 3504: 3496: 3492: 3487: 3482: 3478: 3474: 3470: 3466: 3462: 3455: 3453: 3444: 3440: 3435: 3430: 3426: 3422: 3418: 3414: 3410: 3403: 3395: 3391: 3387: 3383: 3379: 3375: 3368: 3360: 3356: 3352: 3348: 3345:(1): 163–80. 3344: 3340: 3333: 3331: 3322: 3318: 3313: 3308: 3303: 3298: 3294: 3290: 3286: 3279: 3271: 3267: 3263: 3259: 3255: 3251: 3244: 3236: 3232: 3228: 3224: 3220: 3216: 3209: 3201: 3197: 3193: 3189: 3185: 3181: 3177: 3173: 3169: 3165: 3158: 3150: 3146: 3142: 3138: 3135:(11): 443–7. 3134: 3130: 3123: 3115: 3111: 3106: 3101: 3097: 3093: 3089: 3085: 3081: 3074: 3072: 3063: 3059: 3055: 3051: 3046: 3041: 3037: 3033: 3029: 3022: 3014: 3010: 3005: 3000: 2995: 2990: 2986: 2982: 2978: 2971: 2963: 2957: 2953: 2952: 2944: 2936: 2932: 2927: 2922: 2918: 2914: 2911:(10): 740–7. 2910: 2906: 2902: 2895: 2887: 2883: 2879: 2875: 2871: 2867: 2863: 2859: 2852: 2850: 2848: 2836: 2830: 2822: 2818: 2813: 2808: 2805:(5): 849–55. 2804: 2800: 2796: 2789: 2781: 2777: 2772: 2767: 2763: 2759: 2755: 2748: 2740: 2736: 2732: 2728: 2724: 2720: 2716: 2712: 2708: 2704: 2697: 2689: 2685: 2680: 2675: 2671: 2667: 2664:(8): R304-7. 2663: 2659: 2655: 2648: 2646: 2637: 2633: 2628: 2623: 2619: 2615: 2612:(2): 300–72. 2611: 2607: 2603: 2596: 2588: 2584: 2579: 2574: 2570: 2566: 2562: 2555: 2547: 2543: 2538: 2533: 2529: 2525: 2521: 2514: 2512: 2503: 2499: 2495: 2491: 2487: 2483: 2479: 2475: 2471: 2467: 2460: 2452: 2448: 2444: 2440: 2435: 2430: 2427:(7): 811–27. 2426: 2422: 2421:FASEB Journal 2418: 2411: 2403: 2399: 2395: 2391: 2387: 2383: 2379: 2375: 2368: 2360: 2356: 2351: 2346: 2342: 2338: 2334: 2330: 2326: 2322: 2318: 2311: 2303: 2299: 2295: 2291: 2287: 2283: 2279: 2275: 2268: 2260: 2256: 2252: 2248: 2244: 2240: 2233: 2225: 2221: 2217: 2213: 2209: 2205: 2198: 2190: 2186: 2181: 2176: 2171: 2166: 2162: 2158: 2154: 2150: 2146: 2139: 2131: 2127: 2123: 2119: 2115: 2111: 2108:(4): 240–51. 2107: 2103: 2096: 2088: 2084: 2079: 2074: 2071:(7): R236-9. 2070: 2066: 2062: 2055: 2047: 2043: 2038: 2033: 2029: 2025: 2021: 2017: 2013: 2006: 1996: 1988: 1984: 1980: 1976: 1972: 1968: 1965:(9): 515–27. 1964: 1960: 1953: 1945: 1939: 1935: 1934: 1926: 1918: 1912: 1908: 1907: 1899: 1891: 1887: 1883: 1879: 1875: 1871: 1868:(2): 99–111. 1867: 1863: 1856: 1848: 1846:9780123741455 1842: 1838: 1831: 1827: 1818: 1815: 1813: 1810: 1808: 1805: 1803: 1800: 1798: 1795: 1793: 1790: 1788: 1785: 1783: 1780: 1778: 1775: 1774: 1768: 1764: 1761: 1755: 1752: 1748: 1744: 1739: 1737: 1732: 1728: 1723: 1721: 1717: 1713: 1708: 1702: 1696: 1694: 1693:review papers 1690: 1686: 1682: 1678: 1674: 1670: 1666: 1662: 1657: 1655: 1651: 1647: 1643: 1639: 1635: 1631: 1627: 1626:Stanley Cohen 1623: 1620:in 1954, and 1619: 1615: 1610: 1608: 1604: 1600: 1596: 1592: 1588: 1584: 1580: 1576: 1568: 1563: 1550: 1546: 1542: 1539:, particular 1538: 1526: 1514: 1510: 1506: 1503: 1499: 1492: 1489: 1485: 1481: 1478: 1475: 1471: 1470:cell division 1467: 1463: 1459: 1455: 1451: 1448: 1447: 1446: 1439: 1431: 1426: 1416: 1410: 1407: 1402: 1398: 1395:For example, 1392: 1389: 1382: 1381: 1379: 1378: 1377: 1374: 1370: 1369:growth factor 1365: 1363: 1359: 1348: 1346: 1342: 1338: 1334: 1330: 1326: 1316: 1314: 1311:, and penile 1310: 1306: 1302: 1298: 1294: 1290: 1280: 1278: 1274: 1270: 1260: 1258: 1253: 1251: 1246: 1238: 1235: 1231: 1227: 1223: 1215: 1211: 1207: 1203: 1193: 1188: 1178: 1176: 1175:interleukin-1 1172: 1168: 1164: 1160: 1156: 1152: 1148: 1144: 1140: 1135: 1133: 1132:prostaglandin 1129: 1125: 1121: 1117: 1115: 1111: 1106: 1102: 1098: 1094: 1090: 1086: 1084: 1080: 1075: 1070: 1068: 1064: 1060: 1055: 1053: 1049: 1045: 1041: 1037: 1033: 1029: 1023: 1013: 1011: 1005: 1003: 999: 992: 982: 980: 976: 972: 968: 964: 960: 956: 952: 948: 942: 932: 930: 926: 922: 921: 914: 912: 908: 904: 900: 896: 891: 889: 885: 884:proliferation 881: 877: 873: 869: 865: 857: 852: 847: 837: 834: 830: 828: 824: 820: 816: 811: 807: 803: 799: 794: 793: 789: 788:pseudokinases 785: 781: 777: 773: 769: 765: 761: 757: 753: 749: 745: 744:growth factor 741: 737: 733: 724: 722: 718: 714: 710: 705: 703: 699: 693: 691: 687: 684: 683: 682:Dictyostelium 678: 674: 670: 666: 662: 658: 657:secretin-like 654: 650: 644: 634: 632: 628: 620: 616: 612: 608: 603: 600: 596: 589: 585: 581: 577: 573: 568: 565: 560: 556: 546: 544: 543:extracellular 540: 539:intracellular 530: 528: 524: 520: 516: 512: 508: 504: 500: 496: 492: 488: 484: 478: 468: 466: 462: 458: 455: 451: 447: 443: 440: 436: 432: 428: 422: 421:Thermoception 412: 410: 406: 401: 397: 393: 387: 377: 375: 371: 367: 363: 359: 355: 351: 347: 343: 339: 336: 332: 328: 324: 320: 316: 310: 300: 298: 294: 289: 285: 280: 278: 274: 270: 266: 262: 261:neuropeptides 258: 254: 249: 247: 243: 239: 235: 231: 227: 223: 219: 215: 211: 207: 203: 199: 195: 188: 178: 176: 172: 168: 164: 161: 157: 147: 142: 128: 124: 122: 118: 114: 110: 106: 102: 98: 94: 90: 85: 83: 79: 75: 71: 67: 63: 62:transcription 57: 55: 51: 47: 43: 39: 33: 19: 6325:Cell biology 6277:Gap junction 6112:Ca signaling 6075:Cell surface 5930: 5883: 5818: 5797: 5433:eIF-2 kinase 4881: 4756:LitInspector 4726: 4720: 4714:TRANSPATH(R) 4680: 4671: 4662: 4645: 4635: 4626: 4616: 4607: 4598: 4589: 4579: 4570: 4561: 4552: 4542: 4533: 4514: 4508: 4473: 4469: 4459: 4429:(1): 69–77. 4426: 4422: 4416: 4384:(3): 701–7. 4381: 4377: 4367: 4342: 4338: 4332: 4315: 4309: 4268: 4264: 4246: 4213: 4209: 4203: 4171:(6): 490–6. 4168: 4165:EMBO Reports 4164: 4154: 4121: 4077: 4073: 4067: 4032: 4028: 4018: 3985: 3981: 3975: 3948: 3945:FEBS Letters 3944: 3934: 3901: 3897: 3861: 3857: 3847: 3822: 3818: 3812: 3787: 3783: 3776: 3757: 3723: 3719: 3713: 3672: 3668: 3662: 3629: 3625: 3619: 3576: 3572: 3562: 3517: 3513: 3503: 3468: 3464: 3416: 3412: 3402: 3377: 3373: 3367: 3342: 3338: 3292: 3288: 3278: 3253: 3249: 3243: 3218: 3214: 3208: 3167: 3163: 3157: 3132: 3128: 3122: 3087: 3084:Biochemistry 3083: 3035: 3031: 3021: 2984: 2980: 2970: 2951:Biochemistry 2950: 2943: 2908: 2904: 2894: 2861: 2857: 2829: 2802: 2798: 2788: 2761: 2757: 2747: 2706: 2702: 2696: 2661: 2657: 2609: 2605: 2595: 2568: 2564: 2554: 2527: 2523: 2469: 2465: 2459: 2424: 2420: 2410: 2377: 2373: 2367: 2324: 2320: 2310: 2277: 2273: 2267: 2242: 2238: 2232: 2207: 2203: 2197: 2152: 2148: 2138: 2105: 2101: 2095: 2068: 2064: 2054: 2019: 2015: 2005: 1995: 1962: 1958: 1952: 1932: 1925: 1905: 1898: 1865: 1861: 1855: 1836: 1830: 1787:Biosemiotics 1765: 1756: 1740: 1724: 1709: 1705: 1688: 1684: 1658: 1611: 1572: 1502:phospholipid 1498:/DAG pathway 1444: 1414: 1366: 1354: 1322: 1289:free radical 1286: 1283:Nitric oxide 1266: 1254: 1250:calreticulin 1214:mitochondria 1199: 1190: 1136: 1118: 1087: 1079:dimerization 1074:zinc fingers 1071: 1056: 1044:progesterone 1040:testosterone 1025: 1006: 994: 944: 924: 918: 915: 892: 861: 855: 831: 795: 730: 706: 702:ion channels 694: 680: 646: 604: 580:phosphatases 569: 564:conformation 552: 536: 519:photopigment 481:In mammals, 480: 456: 424: 398:between the 389: 386:Osmoreceptor 338:cytoskeleton 312: 287: 281: 250: 193: 190: 152: 108: 100: 96: 92: 86: 58: 37: 36: 6188:By distance 6126:Assistants: 6085:Co-receptor 5120:GNA15/GNA16 4906:Calcineurin 3726:(1): 10–6. 3380:(1): 1–25. 3256:(1): 1–11. 1527:. IP 1358:neutrophils 1297:NO synthase 1155:RIP2 kinase 868:fibronectin 719:due to the 613:domains of 567:cytoplasm. 545:receptors. 461:prokaryotes 415:Temperature 319:Eumetazoans 269:epinephrine 218:fibronectin 160:replicative 91:are termed 74:cell growth 66:translation 6314:Categories 6255:Pheromones 6195:Juxtacrine 5526:Lim kinase 5477:IκB kinase 4998:Transducin 2000:35:1902-22 1823:References 1701:Immunology 1638:cyclic AMP 1511:(DAG) and 1329:superoxide 1143:eukaryotic 911:thrombosis 899:leukocytes 823:expression 776:metabolism 721:expression 673:smoothened 615:calmodulin 588:cyclic AMP 572:eukaryotic 523:melanopsin 515:cone cells 465:eukaryotes 396:osmolarity 380:Osmolarity 323:attachment 265:endorphins 222:hyaluronan 78:metabolism 6209:Endocrine 6204:Paracrine 6200:Autocrine 6067:Receptors 6047:Cytokines 5884:see also 5790:Apoptosis 5271:Monomeric 5003:Gustducin 4921:G protein 4640:2285-2291 4102:205383514 2402:205225137 1743:basophils 1673:G-protein 1659:In 1970, 1650:paracrine 1646:autocrine 1537:receptors 1462:receptors 1373:apoptosis 1313:erections 1309:apoptosis 1237:ryanodine 1222:-receptor 1204:into the 1171:cytokines 1124:precursor 1114:crosstalk 1093:chaperone 1050:into the 1038:hormones 979:induction 907:platelets 880:apoptosis 840:Integrins 827:oncogenes 810:isoprenyl 713:chemokine 649:G protein 533:Receptors 507:rhodopsin 354:selectins 350:cadherins 226:integrins 206:cytokines 46:receptors 6029:Hormones 5979:JAK-STAT 5967:MAPK/ERK 5962:TGF beta 5742:Tyrosine 5687:Arginine 5604:Tyrosine 4817:PATHWAY 4807:Archived 4791:Archived 4773:Archived 4759:Archived 4746:Archived 4721:Science' 4700:Archived 4500:29355685 4451:62775788 4230:11283321 4195:15940278 4094:15286780 4059:16293107 4010:25515586 4002:10707088 3967:16678165 3839:19735727 3804:25422863 3740:17126540 3705:16163262 3697:12447441 3654:13016860 3646:14556004 3611:19276476 3603:12855817 3554:17360592 3495:27208244 3443:21398259 3394:16725254 3359:17084981 3321:12372152 3270:15158434 3235:24818526 3200:26554314 3192:12471243 3114:16700535 3062:45743458 3054:10438939 3013:17203515 2935:21873996 2878:15687224 2821:17351786 2780:16269358 2731:16554823 2688:23618661 2636:12040128 2587:18003769 2546:21852585 2494:16079835 2451:21267494 2443:16675838 2394:21654799 2359:23000897 2224:11826268 2189:12606724 2130:20654561 2102:Steroids 2087:16581495 2046:12169636 1987:35252401 1979:26289315 1882:15654321 1771:See also 1665:glucagon 1603:secretin 1591:hormones 1460:surface 1293:arginine 1273:ceramide 1234:alkaloid 1212:and the 1167:caspases 1063:promoter 872:collagen 846:Integrin 817:such as 764:tyrosine 669:frizzled 665:adhesion 586:such as 489:and the 348:such as 331:integrin 263:such as 257:dopamine 253:odorants 216:such as 163:telomere 117:analysis 6304:Biology 6160:General 5984:Akt/PKB 5868:EDARADD 5853:Mucin-4 5592:RPS6KA1 5438:EIF2AK3 4894:Calcium 4727:Science 4621:345-353 4547:211-250 4399:1172772 4324:4621276 4301:5650340 4293:6101906 4273:Bibcode 4238:6747529 4186:1369102 4050:1316260 3926:2442814 3906:Bibcode 3898:Science 3880:8021233 3677:Bibcode 3581:Bibcode 3573:Science 3545:1838668 3522:Bibcode 3486:4902592 3434:3091050 3172:Bibcode 3164:Science 3149:3075366 3105:4301406 3004:4087537 2926:3177959 2886:7938806 2739:4311262 2711:Bibcode 2679:3685181 2502:4374012 2474:Bibcode 2350:3465532 2329:Bibcode 2282:Bibcode 2274:Science 2259:9457173 2157:Bibcode 2122:8733009 1933:Biology 1890:3065483 1607:insulin 1583:thyroid 1567:MEDLINE 1557:History 1549:calcium 1543:in the 1525:cytosol 1466:protein 1206:cytosol 1196:Calcium 1128:retinol 1052:nucleus 1036:steroid 998:synapse 858:(2007). 754:in the 740:ligands 611:EF hand 497:in the 400:cytosol 374:balance 362:hearing 333:-bound 181:Ligands 135:Stimuli 121:disease 89:Ligands 6290:Portal 6013:Agents 5873:PRKCSH 5712:Other 5661:DYRK1B 5656:DYRK1A 5396:Other 5366:Cyclin 5349:Cyclin 4739:(MeSH) 4521: 4498: 4492:376714 4490: 4449: 4443:857951 4441: 4408:782447 4406: 4396: 4359:169771 4357: 4322: 4299: 4291: 4265:Nature 4236: 4228: 4193: 4183: 4130: 4100: 4092: 4057: 4047: 4008: 4000: 3965: 3924: 3878: 3837: 3802: 3764: 3738: 3703: 3695: 3669:Nature 3652: 3644: 3609: 3601: 3552: 3542: 3493: 3483: 3441: 3431: 3392: 3357: 3319: 3312:244915 3309: 3268: 3233: 3198: 3190: 3147: 3112: 3102: 3060: 3052: 3011: 3001: 2958: 2933: 2923: 2884: 2876: 2819: 2778: 2758:Neuron 2737: 2729: 2703:Nature 2686: 2676: 2634: 2627:120784 2624: 2585: 2544: 2500: 2492: 2466:Nature 2449: 2441: 2400: 2392: 2374:Nature 2357: 2347: 2321:Nature 2302:959823 2300: 2257: 2222: 2187: 2180:151311 2177: 2128: 2120: 2085: 2044: 2037:126171 2034: 1985: 1977: 1940: 1913: 1888: 1880: 1843: 1760:DeLisi 1751:ligand 1731:B cell 1581:, the 1579:spleen 1474:cancer 1390:(PTM)) 1339:, and 1305:stroke 1110:serine 973:, and 957:, and 886:, and 856:et al. 792:kinome 752:dimers 736:kinase 503:retina 297:cancer 171:neuron 167:senses 115:, the 6175:TFIIH 6170:TFIID 5994:Hippo 5974:Notch 5831:Other 5769:both: 5676:DYRK4 5671:DYRK3 5666:DYRK2 5628:PTK2B 5613:ZAP70 5580:ROCK2 5575:ROCK1 5536:LIMK2 5531:LIMK1 5519:IRAK4 5514:IRAK3 5509:IRAK2 5504:IRAK1 5492:IKBKG 5470:GSK3B 5465:GSK3A 5460:GSK-3 5375:Lipid 5326:Rhebs 5237:BSCL2 5232:GNG13 5227:GNG12 5222:GNG11 5217:GNG10 5182:GNGT2 5177:GNGT1 5115:GNA14 5110:GNA13 5105:GNA12 5100:GNA11 5075:GNAT3 5070:GNAT2 5065:GNAT1 5060:GNAI3 5055:GNAI2 5050:GNAI1 5045:GNAO1 4496:S2CID 4447:S2CID 4297:S2CID 4234:S2CID 4098:S2CID 4006:S2CID 3701:S2CID 3650:S2CID 3607:S2CID 3196:S2CID 3058:S2CID 2882:S2CID 2838:(PDF) 2735:S2CID 2498:S2CID 2447:S2CID 2398:S2CID 2126:S2CID 1983:S2CID 1886:S2CID 1679:with 1593:" by 1173:like 1163:NALP3 1159:NF-κB 1126:like 967:IRAK4 963:IRAK1 951:TIRAP 947:Myd88 621:. PIP 487:sight 483:light 471:Light 454:ncRNA 450:Hsp90 446:Hsp70 442:Hsp40 366:touch 335:actin 293:EGFRs 5945:GPCR 5819:see 5798:see 5699:McsB 5623:PTK2 5563:PAK4 5558:PAK3 5553:PAK2 5548:PAK1 5487:IKK2 5482:CHUK 5455:GSK2 5450:GSK1 5336:RGKs 5331:Raps 5316:Arfs 5311:Rhos 5304:NRAS 5299:KRAS 5294:HRAS 5284:Rabs 5279:ARFs 5212:GNG8 5207:GNG7 5202:GNG5 5197:GNG4 5192:GNG3 5187:GNG2 5164:GNB5 5159:GNB4 5154:GNB3 5149:GNB2 5144:GNB1 5095:GNAQ 5090:GNAL 5085:GNAS 5080:GNAZ 5013:cGMP 4989:cGMP 4969:cAMP 4939:cAMP 4882:see 4815:KEGG 4519:ISBN 4488:PMID 4439:PMID 4404:PMID 4355:PMID 4320:PMID 4289:PMID 4226:PMID 4191:PMID 4128:ISBN 4090:PMID 4055:PMID 3998:PMID 3963:PMID 3922:PMID 3876:PMID 3835:PMID 3800:PMID 3762:ISBN 3736:PMID 3693:PMID 3642:PMID 3599:PMID 3550:PMID 3491:PMID 3439:PMID 3390:PMID 3355:PMID 3343:1775 3317:PMID 3266:PMID 3231:PMID 3188:PMID 3145:PMID 3110:PMID 3050:PMID 3009:PMID 2956:ISBN 2931:PMID 2874:PMID 2817:PMID 2776:PMID 2727:PMID 2684:PMID 2632:PMID 2583:PMID 2542:PMID 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Index