RGS2/G0S8 is a selective inhibitor of Gqα function

Scott P. Heximer, Ned Watson, Maurine E. Linder, Kendall J. Blumer, John R. Hepler

Research output: Contribution to journalArticlepeer-review

294 Scopus citations

Abstract

RGS (regulators of G protein signaling) proteins are GTPase activating proteins that inhibit signaling by heterotrimeric G proteins. All RGS proteins studied to date act on members of the Giα family, but not Gsα or G12α. RGS4 regulates Giα family members and Gqα. RGS2 (G0S8) is exceptional because of G proteins it regulates have not been identified. We report that RGS2 is a selective and potent inhibitor of Gqα function. RGS2 selectively binds Gqα, but not other Gα proteins (Gi, Go, Gs, G12/13) in brain membranes; RGS4 binds Gqα and Giα family members. RGS2 binds purified recombinant Gqα, but not Goα, whereas RGS4 binds either. RGS2 does not stimulate the GTPase activities of Gsα or Giα family members, even at a protein concentration 3000-fold higher than is sufficient to observe effects of RGS4 on Giα family members. In contrast, RGS2 and RGS4 completely inhibit Gq-directed activation of phospholipase C in cell membranes. When reconstituted with phospholipid vesicles, RGS2 is 10-fold more potent than RGS4 in blocking Gqα-directed activation of phospholipase Cβ1. These results identify a clear physiological role for RGS2, and describe the first example of an RGS protein that is a selective inhibitor of Gqα function.

Original languageEnglish
Pages (from-to)14389-14393
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number26
DOIs
StatePublished - Dec 23 1997

Keywords

  • Phosphoinositide hydrolysis
  • Phospholipase C-β
  • Regulator of G protein signaling

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