GTP-binding

G-Protein Coupling. The heterotrimeric guanosine triphosphate (GTP) binding proteins, known as G-proteins, are a principal family of proteins serving to couple membrane receptors of the G-protein family to ionic and biochemical processes. This topic is reviewed in References 63—67. 

Five of the six loop regions (G1-G5 in Figure 13.4) that are present at the carboxy end of the p sheet in the Ras structure participate in the GTP binding site. Three of these loops, G1 (residues 10-17), G3 (57-60), and G4 (116-119), contain regions of amino acid sequence conserved among small GTP-binding proteins and the Ga subunits of trimerlc G proteins. 

Binding to Gpy locks the flexible switch regions I and II of Ga into a conformation that firmly binds GDP but is nonproductive for GTP binding and hydrolysis. The replacement of GDP with GTP causes local but dramatic conformational changes to switch regions I and 11, as shown in the Go GTP-yS structure, which disrupt nearly all of the contacts between Gp. and Ga in the switch interface, thereby triggering release of Ga from Gpy (see Figures 13.10 and 13.11). 

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... 

Costa, T., and Herz, A. (1989). Antagonists with negative intrinsic activity at 6-opioid receptors coupled to GTP-binding proteins. Proc. Natl. Acad. Sci. U.S.A. 86 7321-7325. 

GTP-binding protein at an arginine residue which is involved in GTP hydrolysis. ADP-ribosylation thus leads to constitutive activation of Gs. 

Heterotrimeric GTP-binding Proteins Small GTPases Bacterial Toxins... 

In general terms, cross talk refers to the interaction between signalling pathways, e.g. between pathways involving heterotrimeric GTP-binding proteins and tyrosine kinase pathways. 

S-acylated proteins include many GTP-binding regulatory proteins (G proteins), including most a subunits of heterotrimeric G-proteins and also many members of the Ras superfamily of monomeric G proteins, a number of G protein-coupled receptors, several nonreceptor tyrosine kinases, and a number of other signaling molecules, -acylation is posttranslational and reversible, a property that allows the cell to control... 

Histidine phosphatases and aspartate phosphatases are well established in lower organisms, mainly in bacteria and in context with two-component-systems . Reversible phosphorylation of histidine residues in vertebrates is in its infancy. The first protein histidine phosphatase (PHP) from mammalian origin was identified just recently. The soluble 14 kD protein does not resemble any of the other phosphatases. ATP-citrate lyase and the (3-subunit of heterotrimeric GTP-binding proteins are substrates of PHP thus touching both, metabolic pathways and signal transduction [4]. 

Small GTPases are monomeric 20 to 40 kD GTP-binding proteins that interconvert between an active (GTP-bound) and an inactive (GDP-bound) state. As molecular switches they are involved in the regulation of complex cellular processes. 

The diversity of these subcellular actin structures is remarkable and appears to be determined by the interactions of many actin-binding proteins (ABPs) as well as by changes in the concentrations of intracellular signaling molecules such as Ca and cAMP, by small GTP-binding proteins, and by signals arising from mechanical stress. Approximately 50% of the actin molecules in most animal cells are unpolymerized subunits in the cytosolic pool and exist in a state of dynamic equilibrium with labile F-actin filamentous structures (i.e., new structures are formed while existing structures are renewed) (Hall, 1994). 

Hall, A. (1994). Small GTP-binding proteins and the regulation of the actin cytoskeleton. Ann. Rev. Cell Biol. 10,31-54. 

Ridley, A.J., Hall, A. (1992). The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell 70,389-399. 

LRG ]) provides a preliminary estimate for the bimolecular rate constant of GTPyS binding ( 2 x 10 /ilf s ). This estimate is within an order of magnitude of the rates of GTP binding to another G protein (23). 

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