RGS4 Inhibits Gq-mediated Activation of Mitogen-activated Protein Kinase and Phosphoinositide Synthesis
作者： Yibing Yan , Patty P. Chi , Henry R. Bourne
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摘要: Recombinant regulators of G protein-signaling (RGS) proteins stimulate hydrolysis GTP by α subunits the Gi family but have not been reported to regulate other protein subunits. Expression recombinant RGS in cultured cells inhibits Gi-mediated hormonal signals probably acting as GTPase-activating for Gαisubunits. To ask whether an can also cellular responses mediated Gq/11 family, we compared activation mitogen-activated kinase (MAPK) a Gq/11-coupled receptor, bombesin receptor (BR), and Gi-coupled D2 dopamine transiently co-expressed with or without RGS4 COS-7 cells. Pertussis toxin, which uncouples from receptors, blocked MAPK BR. Co-expression RGS4, however, inhibited both receptors causing rightward shift concentration-effect curve agonists. BR-stimulated synthesis inositol phosphates effector target Gq/11, phospholipase C. Moreover, phosphate activated addition AlF4− overexpressing αq, binding αq·GDP·AlF4−. These results demonstrate that Gq/11-mediated competing well protein.
highwire.org参考文章(21)
B R Conklin, O Chabre, Y H Wong, A D Federman, H R Bourne, Recombinant Gq alpha. Mutational activation and coupling to receptors and phospholipase C. Journal of Biological Chemistry. ,vol. 267, pp. 31- 34 ,(1992) , 10.1016/S0021-9258(18)48452-9
K.D. Lustig, B.R. Conklin, P. Herzmark, R. Taussig, H.R. Bourne, Type II adenylylcyclase integrates coincident signals from Gs, Gi, and Gq. Journal of Biological Chemistry. ,vol. 268, pp. 13900- 13905 ,(1993) , 10.1016/S0021-9258(19)85187-6
M. Faure, T.A. Voyno-Yasenetskaya, H.R. Bourne, cAMP and beta gamma subunits of heterotrimeric G proteins stimulate the mitogen-activated protein kinase pathway in COS-7 cells. Journal of Biological Chemistry. ,vol. 269, pp. 7851- 7854 ,(1994) , 10.1016/S0021-9258(17)37127-2
J. R. Hepler, D. M. Berman, A. G. Gilman, T. Kozasa, RGS4 and GAIP are GTPase-activating proteins for Gqα and block activation of phospholipase Cβ by γ-thio-GTP-Gqα Proceedings of the National Academy of Sciences of the United States of America. ,vol. 94, pp. 428- 432 ,(1997) , 10.1073/PNAS.94.2.428
Kirk M. Druey, Kendall J. Blumer, Veronica H. Kang, John H. Kehrl, Inhibition of G-protein-mediated MAP kinase activation by a new mammalian gene family Nature. ,vol. 379, pp. 742- 746 ,(1996) , 10.1038/379742A0
Henry R. Bourne, David A. Sanders, Frank McCormick, The GTPase superfamily: a conserved switch for diverse cell functions Nature. ,vol. 348, pp. 125- 132 ,(1990) , 10.1038/348125A0
David M Berman, Thomas M Wilkie, Alfred G Gilman, GAIP and RGS4 Are GTPase-Activating Proteins for the Gi Subfamily of G Protein α Subunits Cell. ,vol. 86, pp. 445- 452 ,(1996) , 10.1016/S0092-8674(00)80117-8
Gabriel Berstein, Jonathan L. Blank, Deok-Young Jhon, John H. Exton, Sue Goo Rhee, Elliott M. Ross, Phospholipase C-β1 is a GTPase-activating protein for Gq/11, its physiologic regulator Cell. ,vol. 70, pp. 411- 418 ,(1992) , 10.1016/0092-8674(92)90165-9
Vadim Yu. Arshavsky, M. Deric Bownds, Regulation of deactivation of photoreceptor G protein by its target enzyme and cGMP. Nature. ,vol. 357, pp. 416- 417 ,(1992) , 10.1038/357416A0
Timothy W. Hunt, Timothy A. Fields, Patrick J. Casey, Ernest G. Peralta, RGS10 is a selective activator of G alpha i GTPase activity. Nature. ,vol. 383, pp. 175- 177 ,(1996) , 10.1038/383175A0