Receptor guanine nucleotide protein-coupled

G-proteins are trimeric, signal-transducing, guanine nucleotide-binding proteins. They constitute the first step in transducing the agonist-induced activation of a G-protein-coupled receptor (see Chapter 2) to a cellular response. 

Figure 2.5. The synapse. GPCR = guanine nucleotide-binding protein-coupled receptor, LGICR = ligand-gated ion channel receptor, SB = synaptic bouton, T = neurotransmitter, YOC = voltage-operated ion channel protein, YOCC = voltage-operated calcium channel protein, Ast = astrocyte, AA = axoaxonal synapse, ASD = axosomatic or axodendritic synapse. GPCR 1 = receptor protein, 2 = G-protein, 3 = enzyme, 4 = ion channel protein.

Fig. 3 A AGS proteins isolated in yeast-based functional screen G-protein signaling modulator (GPSM) as named by the Human Genome Nomenclature Committee. The major sites of action of AGS proteins in the context of the G-protein activation-deactivation cycle are indicated B on the right. (GPR G-protein regulatory, GEF guanine nucleotide exchange factor, GDI guanine nucleotide dissociation inhibitor, GPCR G-protein coupled receptor)...

The G proteins with which G protein-coupled receptors interact are heterotrimeric complexes composed of a, P, and y subunits. In its inactive state, the G-protein a subunit is bound to GDP and associates with a Py dimer. Upon receptor activation, the a subunit opens its guanine nucleotide binding site and releases its bound GDP, allowing GTP, which is present in higher concentrations in the cell, to bind in its place. The GTP-bound a subunit has a lower affinity for the Py dimer and dissociates from it, freeing both the a sub-... 

Fig. 9.1. The Ras protein as a central switching station of signaling pathways. A main pathway for Ras activation is via receptor tyrosine kinases, which pass the signal on via adaptor proteins and guanine nucleotide exchange factors to the Ras protein. Activation ofRas protein can also be initiated via G-protein-coupled receptors and via transmembrane receptors with associated tyrosine kinase activity. The membrane association of the Ras protein (see Fig. 9.6) is not shown for clarity. In addition, not aU signahng pathways that contribute to activation of the Ras protein are shown, nor are all effector reactions. Py omplex of the heterotrimeric G proteins GAP GTPase activating protein GEF guanine nucleotide exchange factor.

G protein-coupled receptors linked to a second messenger system by a guanine nucleotide protein. 

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... 

Wu, Y., Buranda, T., Simons, P. C., Lopez, G. P., Mclntire, W. E., Garrison, J. C., Prossnitz, E. R., and Sklar, L. A. (2007a). Rapid mix flow cytometry measurements of subsecond regulation of G protein-coupled receptor ternary complex dynamics by guanine nucleotides. Anal. Biochem. In press. 

T4. Thelen, M., Wymann, M. P., and Langen, H., Wortmannin binds specifically to 1-pho-sphatidylinositol 3-kinase while inhibiting guanine nucleotide-binding protein-coupled receptor signaling in neutrophil leukocytes. Proc. Natl. Acad. Sci. USA 91, 4960-4964 (1994). 

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