Guanosine triphosphate-binding protein

Maridonneau-Parini, I., Yang, C.-Z., Bomens, M., Goud, B. (1991). Increase in the expression of a family of small guanosine triphosphate-binding proteins, rab proteins, during induced phagocyte differentiation. J. Clin. Invest. 87,901-7. 

Hammond HR, Roth DA, McKirnan MD, Ping P. 1993. Regional myocardial down regulation of the inhibitory guanosine triphosphate binding protein (Gi alpha 2) and beta-adrenergic receptos in a porcine model of chronic myocardial ischemia. J Clin Invest 92 2644-2652. 

Longabaugh JP, Vatner DE, Vatner SF, Homey CJ. 1988. Decreased stimulatory guanosine triphosphate binding protein in dogs with pressure-overload left ventricular failure. J Clin Invest 81 420—424. 

The presence of a nitrogen-containing side chain facilitates interaction with the catalytic site of FPPS, an enzyme in the metabolic pathway that is required for the production of the isoprenoid hpids farnesyl diphosphate and geranylgeranyl diphosphate, essential metabolites for posttranslational protein prenylation [5, 8]. Inhibiting the prenylation of guanosine triphosphate-binding proteins such as Ras, Rho, and Rac disrupts the normal cellular signal transduction that is required for osteoclast function and survival [5]. 

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. 

Synthesized by soluble guanylyl cyclase and particulate guanylyl cyclase from guanosine triphosphate (GTP). Nitric oxide activates soluble guanylyl cyclase to enhance cyclic GMP production that contributes to various NO actions. Cyclic GMP is hydrolyzed by phosphodiesterases. Cyclic GMP binds to and activates cGMP-dependent protein kinase, phosphodiesterases, and Cyclic Nucleotide-regulated Cation Channels. 

Finally, it may be possible to obtain some limited information on the mechanisms of action of agonists from the shapes of binding curves. For example, as discussed later, the binding of some agonists is affected by guanosine triphosphate (GTP), immediately suggesting the involvement of G-proteins in the transduction mechanism. 

G proteins comprise several families of diverse cellular proteins that subserve an equally diverse array of cellular functions. These proteins derive their name from the fact that they bind the guanine nucleotides guanosine triphosphate (GTP) and guanosine diphosphate (GDP) and possess intrinsic GTPase activity. G proteins play a central role in signal transduction as well as in a myriad of cellular processes, including membrane vesicle transport,... 

All GTP binding proteins in signal transduction share a common structural element - the Ras-like domain which is responsible for the specific complexation of guanosine diphosphate and -triphosphate and which contains catalytic residues that promote GTP-hydrolysis. 

Adlersberg M, Arango V, Hsiung S, Mann JJ, Underwood MD, et al. 2000. In vitro autoradiography of serotonin 5-HT (2A/2C) receptor-activated G protein guanosine-5 -(gamma-[(35)S]thio)triphosphate binding in rat brain, J Neurosci Res 61 674-685. 

Such differences have been ascribed to the fact that the cyclase is linked to two distinct guanosine triphosphate (GTP) binding proteins in the cell membrane, termed Gi and Gs. The former protein inhibits the cyclase, possibly by reducing the effects of the Gs protein which stimulates the cyclase. The relationship between the posts)maptic receptor and the second messenger system is illustrated in Figure 2.4. 

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