He, Wei and Lu, Lisha and Zhang, Xue and El-Hodiri, Heithem M. and Chen, Ching-Kang and Slep, Kevin C. and Simon, Melvin I. and Jamrich, Milan and Wensel, Theodore G. (2000) Modules in the photoreceptor RGS9-1•Gβ5L GTPase-accelerating protein complex control effector coupling, GTPase acceleration, protein folding, and stability. Journal of Biological Chemistry, 275 (47). pp. 37093-37100. ISSN 0021-9258. http://resolver.caltech.edu/CaltechAUTHORS:HEWjbc00
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RGS (regulators of G protein signaling proteins regulate G protein signaling by accelerating GTP hydrolysis, but little is known about regulation of GTPase-accelerating protein (GAP) activities or roles of domains and subunits outside the catalytic cores. RGS9-1 is the GAP required for rapid recovery of light responses in vertebrate photoreceptors and the only mammalian RGS protein with a defined physiological function. It belongs to an RGS subfamily whose members have multiple domains, including G gamma -like domains that bind G(beta5) proteins. Members of this subfamily play important roles in neuronal signaling, Within the GAP complex organized around the RGS domain of RGS9-1, we have identified a functional role for the G gamma -like-G(beta 5L) complex in regulation of GAP activity by an effector subunit, cGMP phosphodiesterase gamma and in protein folding and stability of RGS9-1, The C-terminal domain of RGS9-1 also plays a major role in conferring effector stimulation. The sequence of the RGS domain determines whether the sign of the effector effect will be positive or negative. These roles were observed in, vitro using full-length proteins or fragments for RGS9-1, RGS7, G(beta 5S), and G(beta 5s), The dependence of RGS9-1 on Gp, co-expression for folding, stability, and function has been confirmed in vivo using transgenic Xenopus laevis, These results reveal how multiple domains and regulatory polypeptides work together to fine tune G(t alpha) inactivation.
|Additional Information:||© 2000 by the American Society for Biochemistry and Molecular Biology. Received for publication, August 2, 2000, and in revised form, August 31, 2000. Originally published In Press as doi:10.1074/jbc.M006982200 on September 7, 2000. We thank J. Gray, L. Zimmerman, M. Offield, and R. Grainger for advice on transgenesis and F. He for help in expression and purification of proteins from E. coli. This work was supported by grants from the National Institutes of Health and by the Robert A. Welch Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.|
|Subject Keywords:||RGS PROTEINS; BETA-SUBUNIT; TARGET ENZYME; GAMMA; TRANSDUCIN; DOMAIN; DEACTIVATION; EXPRESSION; REGULATORS; DISTINCT|
|Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Tony Diaz|
|Deposited On:||17 Sep 2008 05:21|
|Last Modified:||26 Dec 2012 10:17|
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