Signal pathway-associated protein

The main function of lipidation is to promote membrane association of signaling proteins. Lipid anchors target proteins to the membrane, as is the case for the cytoplasmic protein tyrosine kinases, so that they can participate in membrane-associated signaling pathways. Furthermore, protein lipidation is thought to mediate protein-protein association and/or stabilize protein conformations (review Casey, 1995). 

The transformation of rodent fibroblasts by a variety of tyrosine kinase oncogenes also causes chronic elevation of Ras-GTP levels. It thus seems obvious that Ras proteins ate essential components of tyrosine kinase mediated rtritogenic signaling pathways. Ras proteins are activated in response to a wide variety of extracellular stimuli that activate receptor and receptor-associated tyrosine kinases TKs). 

Figure 7. Schematic of a receptor with intrinsic enzymatic activity. Ligand mediated activation results in phosphorylation of phospholipase C (y isoform) leading to hydrolysis of polyphosphoinositides (PIP2). Dia-cyl-glycerol (DAG) and inositol-triphosphate (IP3) are formed. 1P3 increases the release of stored calcium. Calcium together with DAG can activate PKC signalling pathway. Association of this type of receptor with adapter proteins results in activation of Ras/Raf/ERK signalling or in activation of PI3K/Akt signalling.

Bouaboula M, Poinot-Chazel C, Marchand J, Canat X, Bourrie B, Rinaldi-Carmona M, Calandra B, Le Fur G, CaseUas P (1996) Signaling pathway associated with stimulation of CB2 peripheral cannabinoid receptor. Involvement of both mitogen-activated protein kinase and induction of Krox-24 expression. Eur J Biochem 237 704-711... 

Fig. 11.12 Overview of signaling pathways associated with activation of lymphocytes. The triggering signal for activation of T lymphocytes is generally antigen binding to the Tcell receptor. The activated receptor passes the signal on to associated tyrosine kinases like Fyn, Lck and ZAP70. These phospho-rylate the transmembrane protein LAT on cytoplasmic tyrosine residues. The LAT phospho-tyro-sine residues are docking sites for adaptors ( She,...

The hormonal stimulation of adenylyl cyclase is effected by a transmembrane signaling pathway consisting of three components, all membrane-associated. Binding of hormone to the external surface of a hormone receptor causes a conformational change in this transmembrane protein, which in turn stimulates a GTP-binding protein (abbreviated G protein). G proteins are heterotrimeric proteins consisting of a- (45-47 kD), /3- (35 kD), and y- (7-9 kD) subunits. The a-subunit binds GDP or GTP and has an intrinsic, slow... 

Grb-2 facilitates the transduction of an extracellular stimulus to an intracellular signaling pathway, (b) The adaptor protein PSD-95 associates through one of its three PDZ domains with the N-methyl-D-aspartic acid (NMDA) receptor. Another PDZ domain associates with a PDZ domain from neuronal nitric oxide synthase (nNOS). Through its interaction with PSD-95, nNOS is localized to the NMDA receptor. Stimulation by glutamate induces an influx of calcium, which activates nNOS, resulting in the production of nitric oxide. 

Neurotrophins (NGF brain-derived neurotrophic factor, BDNF neurotrophin-3, NT-3 NT-4 NT-6) are important regulators of neural survival, development, function, and plasticity of the vertebrate nervous system [1]. Neurotrophins generally function as noncovalently associated homodimers. They activate two different classes of receptors, through which signaling pathways can be activated, including those mediated by Ras and members of the cdc42/rac/rho G protein families, MAP kinase, PI-3 kinase, and Jun kinase cascades. 

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