RGS proteins, regulation of G protein signaling

FIGURE 12-14 Self-inactivation of Gs.The steps are further described in the text. The protein s intrinsic GTPase activity, in many cases stimulated by RGS proteins (regulators of G protein signaling), determines how quickly bound GTP is hydrolyzed to GDP and thus how long the G protein remains active. 

Several proteins downregulate signalling by G proteins. The RGS proteins (regulators of G-protein signalling) have already been discussed in this chapter. Phosducin and phos-ducin-like proteins have a comparable role in the visual system, and perhaps elsewhere. Other factors, such as recoverin, intercept Ca + signals and regulate dephosphorylation and resensitization. Both phosducin and recoverin are regulated by phosphorylation. Only the role of phosducin will be considered here. 

Ross, E. M. and Wilkie, T. M. GTPase-activating proteins for heterotrimeric G proteins regulators of G protein signaling (RGS) and RGS-like proteins. Annu. Rev. Biochem. 69 795-827, 2000. 

PEPCK phosphoenolpyruvate carboxykinase RGS regulators of G protein signaling... 

Calo, L. A., Pagnin, E., Davis, P. A., et al. (2004) Increased expression of regulator of G protein signaling-2 (RGS-2) in Bartter s/Gitelman s syndrome. A role in the control of vascular tone and implication for hypertension. J. Clin. Endocrinol. Metab. 89, 4153 157. 

Fig. 6 Proteins with GPR motifs. (RBD Ras binding domain, PTB phosphotyrosine binding domain, RGS regulator of G-protein signaling domain, PDZ PSD95/DLG/ZO-1 domain, cc coiled-coil domain). This figure is adapted from the thesis of Dr. Yuri Peterson...

Recently, it was discovered that G-protein activity is controlled by another class of proteins. These proteins, termed RGS proteins (for regulators of G-protein signaling), enhance the rate of GTP hydrolysis. This activity reduces the amount of time the G-protein a subunit spends in its active GTP-bound conformation, in effect limiting the response to receptor activation. 

Aside from the regulation of G-protein activity by RGS proteins, signaling through G protein-coupled receptors can also be regulated at the level of the receptor itself (see Deutch and Roth, 1999). Such regulation occurs through several well-characterized mechanisms (Fig. 3.3). Within seconds to minutes of agonist acti-... 

Lan, K. L., Zhong, H., Nanamori, M., and Neubig, R. R. (2000). Rapid kinetics of regulator of G-protein signaling (RGS)-mediated Gai and Gao deactivation. Galpha specificity of RGS4 and RGS7. /. Biol. Chem. 275, 33497-33503. 

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