Biochemical characterization of RGS14: RGS14 activity towards G-protein α subunits is independent of its binding to Rap2A

Vivek Mittal, Maurine E. Linder

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

RGS (regulators of G-protein signalling) modulate signalling by acting as GAPs (GTPase-activating proteins) for a subunits of heterotrimeric G-proteins. RGS14 accelerates GTP hydrolysis by G family members through its RGS domain and suppresses guanine nucleotide dissociation from G iα1 and Giα3 subunits through its C-terminal GoLoco domain. Additionally, RGS14 binds the activated forms of the small GTPases Rap1 and Rap2 by virtue of tandem RBDs (Raf-like Ras/Rap binding domains). RGS14 was identified in a screen for Rap2 effectors [Traver, Splingard, Gaudriault and De Gunzburg (2004) Biochem. J. 379, 627-632]. In the present study, we tested whether Rap binding regulates RGS14's biochemical activities. We found that RGS14 activity towards heterotrimeric G-proteins, as either a GAP or a GDI (guanine nucleotide dissociation inhibitor), was unaffected by Rap binding. Extending our biochemical characterization of RGS14, we also examined whether RGS14 can suppress guanine nucleotide exchange on Giα1 in the context of the heterotrimer. We found that a heterotrimer composed of N-myristoylated Giα1 and prenylated Gβγ is resistant to the GDI activity of the GoLoco domain of RGS14. This is consistent with models of GoLoco domain action on free G α and suggests that RGS14 alone cannot induce subunit dissociation to promote receptor-independent activation of G βγ-mediated signalling pathways.

Original languageEnglish (US)
Pages (from-to)309-315
Number of pages7
JournalBiochemical Journal
Volume394
Issue number1
DOIs
StatePublished - Feb 15 2006

Keywords

  • G-protein α subunit
  • GTPase-activating protein
  • Guanine nucleotide dissociation inhibitor (GDI)
  • Lipid modification
  • Rap2A
  • Regulators of G-protein signalling 14 (RGS14)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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