Attenuation of Gi- and Gq-mediated signaling by expression of RGS4 or GAIP in mammalian cells

C. Huang, J. R. Hepler, A. G. Gilman, S. M. Mumby

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Abstract

Protein regulators of G protein signaling (RGS proteins) were discovered as negative regulators of heterotrimeric G protein-mediated signal transduction in yeast and worms. Experiments with purified recombinant proteins in vitro have established that RGS proteins accelerate the GTPase activity of certain G protein α subunits (the reaction responsible for their deactivation); they can also act as effector antagonists. We demonstrate herein that either of two such RGS proteins, RGS4 or GAIP, attenuated signal transduction mediated by endogenous receptors, G proteins, and effectors when stably expressed as tagged proteins in transfected mammalian cells. The pattern of selectivity observed in vivo was similar to that seen in vitro. RGS4 and GAIP both attenuated Gi-mediated inhibition of cAMP synthesis. RGS4 was more effective than GAIP in blocking Gq-mediated activation of phospholipase Cβ.

Original languageEnglish (US)
Pages (from-to)6159-6163
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number12
DOIs
StatePublished - Jun 10 1997

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