Proteins signalling

There are five known classes of enzyme-linked receptors (1) receptor tyrosine kinases, which phosphorylate specific tyrosine residues on intracellular signaling proteins (2) tyrosine kinase-associated receptors, such as the prolactin and growth hormone receptors we have already discussed, which... 

AKAPs are a diverse family of about 75 scaffolding proteins. They are defined by the presence of a structurally conserved protein kinase A (PKA)-binding domain. AKAPs tether PKA and other signalling proteins to cellular compartments and thereby limit and integrate cellular signalling processes at specific sites. This compartmentalization of signalling by AKAPs contributes to the specificity of a cellular response to a given external stimulus (e.g. a particular hormone or neurotransmitter). 

AKAPs Optimise the Limited Repertoire of Cellnlar Signalling Proteins... 

Currently no drugs directly modulating the LDL receptor family are known. The possible use of drugs targeting the LDL receptor family or downstream signaling proteins may be derived from Table 1. 

The Src-homology 2 (SH2) domain is a protein domain of roughly 100 amino acids found in many signaling molecules. It binds to phosphorylated tyrosines, in particular peptide sequences on activated receptor tyrosine kinases or docking proteins. By recognizing specific phosphorylated tyrosines, these small domains serve as modules that enable the proteins that contain them to bind to activated receptor tyrosine kinases or other intracellular signaling proteins that have been transiently phosphorylated on tyrosines. 

SARA is a scaffolding protein that regulates the subcellular localization of inactivated R-Smads, potentially scaffolding the TGF-P receptor kinase to the Smad 2 substrate. Filamins are a family of actin polymerization proteins that also form scaffolds for a range of signaling proteins including SAP kinases such as MKK-4, small GTPases Rho and Ras, as well as Smad 2 and Smad 5. 

Potenza MN, Gold SJ, Roby-Shcmkowitz A, et al Effects of regulators of G protein-signaling proteins on the functional response of the mu-opioid receptor in a mel-anophore-based assay. J Pharmacol Exp Ther 291 482 91, 1999 Quaglio G, Talamini G, Lechi A, et al Study of 2708 heroin-related deaths in northeastern Italy 1985—98 to establish the main causes of death. Addiction 96 1127— 1137, 2001... 

Li XD, Sun L, Seth RB, Pineda G, Chen ZJ (2005) Hepatitis C virus protease NS3/4A cleaves mitochondrial antiviral signaling protein off the mitochondria to evade innate immunity. Proc Natl Acad Sci USA 102 17717-17722... 

Darnell JE Jr, Kerr IM, Stark GR Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 1994 264 l4l5. 

The production of a female-influencing secretion from the chin gland of male Plethodontid salamander (P. jordani) points to a similar extension of function by the acquisition of female olfactory sensitivity to an intercellular signal protein. Female receptivity is enhanced by a male cytokine-like compound of the interleukin-6 family, in its released form. Rollman et al. (1999) note that pheromonal activity is a previously unrecognised function for cytokines. 

Thiazolidinediones are known to increase insulin sensitivity by stimulating peroxisome proliferator-activated receptor gamma (PPAR-y). Stimulation of PPAR-y results in a number of intracellular and extracellular changes, including an increased number of insulin receptors, increased insulin receptor sensitivity, decreased plasma fatty acid levels, and an increase in a host of intracellular signaling proteins that enhance glucose uptake. 

The major 3 -phosphoinositide products of class I PI3Ks are phosphati-dylinositol 3,4,5-trisphosphate [PI(3,4,5)P3, which is formed primarily from phosphorylation of PI(4,5)P2) and its metabolite phosphatidylinositol 3,4-bisphosphate, PI(3,4)P2]. The basal levels of PI(3,4)P2 and PI(3,4,5)P3 in cells are usually in low abundance but can rise sharply after cell stimulation to interact with an array of protein effectors via pleckstrin homology (PH) domains, modular segments of about 100 amino acids found in many signaling proteins. It is these PH-domain-containing proteins that are able to propagate and drive downstream signaling events. 

Koch CA, Anderson D, Moran MF, Ellis C, Pawson T. SH2 and SH3 domains elements that control interactions of cytoplasmic signaling proteins. Science 1991 252 668-674. 

Rottapel, R., Reedijk, M., Williams, D. E., Lyman, S. D., Anderson, D. M., Pawson, T., and Bernstein, A. (1991). The Steel/W transduction pathway kit autophosphorylation and its association with a unique subset of cytoplasmic signaling proteins is induced by the Steel factor. Mol. Cell. Biol. 11 3043-3051. 

Schematic structures of some representative enzyme and adaptor targets for signalling protein tyrosine kinases...

The nonreceptor PTKs are a large group of signaling proteins that have diverse roles in the control of cell proliferation, differentiation, and death. Some are widely expressed others are restricted to particular tissues. Their early classification was dominated by the discovery of pp60src, to the extent that the major group of kinases were simply known as the Src family. There are at least ten known subfamilies of nonreceptor PTKs. 

Raff Isn t this because IGF1 is limiting All extracelluar signal proteins seem to be limiting in tissues. 

Gleeson JG, Allen KM, Fox JW et al 1998 doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein. Cell 92 63-72... 

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