Guanine nucleotide release proteins

Strittmatter SM, Valenzuela D, Sudo Y, Linder ME, Eishman MC (1991) An intracellular guanine nucleotide release protein for Go. GAP-43 stimulates isolated alpha subunits by a novel mechanism. J Biol Chem 266 22465-22471... 

The first step in the activation of G proteins is the replacement of GDP by GTP. Whereas in the case of heterotrimeric G proteins, GDP-GTP exchange is catalysed by G-protein-coupled heptahelical receptors, monomeric G proteins, such as Ras, recruit GDP exchange factors (GEFs) and guanine nucleotide release proteins (GNRPs). These factors promote formation of the active, GTP-bound form of Ras and, because they are linkers, connect Ras with the RTK. 

S. Tanaka, T. Morishita, Y. Hashimoto, S. Hattori, S. Nakamura, M. Shibuya, et cd. C3G, a guanine nucleotide-releasing protein expressed ubiquitously, binds to the Src homology 3 domains of CRK and GRB2/ASH proteins. Proc Natl Acad Set, USA, 91 (8), 3443-3447, 1994. 

Figure 1. Simplified schematic of receptor-mediated signal transduction in neutrophils. Binding of ligand to the receptor activates a guanine-nucleotide-binding protein (G protein), which then stimulates phospholipase C. Phosphatidylinositol 4,5-bis-phosphate is cleaved to produce diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG stimulates protein kinase C. IP3 causes the release of Ca from intracellular stores, which results in an increase in the cytosolic Ca concentration. This increase in Ca may stimulate protein kinase C, calmodulin-dependent protein kinases, and phospholipase A2. Protein phosphorylation events are thought to be important in stimulating degranulation and oxidant production. In addition, ionic fluxes occur across the plasma membrane. It is possible that phospholipase A2 and ionic channels may be governed by G protein interactions. ...

After a neurotransmitter s release and binding to its cognate membranous receptor, a cascade of intracellular processes is induced that coordinate the incoming information. Guanine nucleotide-binding proteins (G proteins] are composed of subunits (a, p, and y] that convey information from the cell sur-... 

Many other receptors are 7-helix transmembrane proteins, which activate guanine nucleotide G proteins (Chapter 11, Section D, 3). The G proteins couple some receptors directly to Ca2+ channels they couple other receptors to adenylate cyclase and cyclic AMP-activated channels and yet others via phospholipase C to K+ channels and indirectly to Ca2+ channels (Fig. 30-19). All of these G protein coupled receptors are referred to as metabotropic receptors. A single synapse often contains both ionotropic receptors and metabotropic receptors. The ionotropic receptors induce a rapid (< 1 ms) response, while the metabotropic receptors act more slowly. However, in most cases the final effect is the release of calcium ions into the cytoplasm... 

Felder CC, Williams HL, Axelrod J (1991) A transduction pathway associated with receptors coupled to the inhibitory guanine nucleotide binding protein Gi that amplifies ATP-mediated arachidonic acid release. Proc Natl Acad Sci USA 53 6477 6480. 

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