The RGS14 GoLoco domain discriminates among Gαi isoforms

Vivek Mittal, Maurine E. Linder

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

Regulators of G protein signaling (RGS) modulate G protein activity by functioning as GTPase-activating proteins (GAPs) for α-subunits of heterotrimeric G proteins. RGS14 regulates G protein nucleotide exchange and hydrolysis by acting as a GAP through its RGS domain and as a guanine nucleotide dissociation inhibitor (GDI) through its GoLoco motif. RGS14 exerts GDI activity on Gαi1, but not Gαo. Selective interactions are mediated by contacts between the αA and αB helices of the Gαi1 helical domain and the GoLoco C terminus (Kimple, R. J., Kimple, M. E., Betts, L., Sondek, J., and Siderovski, D. P. (2002) Nature 416, 878-881). Three isoforms of Gαi exist in mammalian cells. In this study, we tested whether all three isoforms were subject to RGS14 GDI activity. We found that RGS14 inhibits guanine nucleotide exchange on Gαi1 and Gαi3, but not Gαi2. Gαi2 could be rendered sensitive to RGS14 GDI activity by replacement of residues within the α-helical domain. In addition to the contact residues in the αA and αB helices previously identified, we found that the αA/αB and αB/αC loops are important determinants of Gαi selectivity. The striking selectivity observed for RGS14 GDI activity in vitro points to Gαi1 and Gαi3 as the likely targets of RGS14-GoLoco regulation in vivo.

Original languageEnglish (US)
Pages (from-to)46772-46778
Number of pages7
JournalJournal of Biological Chemistry
Volume279
Issue number45
DOIs
StatePublished - Nov 5 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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