Regulation of α 2B-adrenergic receptor-mediated extracellular signal-regulated kinase 1/2 (ERK1/2) activation by ADP-ribosylation factor 1

Chunmin Dong, Chunman Li, Guangyu Wu

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

A number of signaling molecules are involved in the activation of the mitogen-activated protein kinase (MAPK) pathway by G protein-coupled receptors. In this study, we have demonstrated that α 2B-adrenergic receptor (α 2B-AR) interacts with ADP-ribosylation factor 1 (ARF1), a small GTPase involved in vesicle-mediated trafficking, in an agonist activation-dependent manner and that the interaction is mediated through a unique double Trp motif in the third intracellular loop of the receptor. Interestingly, mutation of the double Trp motif and siRNA-mediated depletion of ARF1 attenuate α 2B-AR-mediated activation of extracellular signal-regulated kinases 1/2 (ERK1/2) without altering receptor intracellular trafficking, whereas expression of the constitutively active mutant ARF1Q71L and ARNO, a GDP-GTP exchange factor of ARF1, markedly enhances the activation of Raf1, MEK1, and ERK1/2. These data strongly demonstrate that the small GTPase ARF1 modulates ERK1/2 activation by α 2B-AR and provide the first evidence indicating a novel function for ARF1 in regulating the MAPK signaling pathway.

Original languageEnglish (US)
Pages (from-to)43361-43369
Number of pages9
JournalJournal of Biological Chemistry
Volume286
Issue number50
DOIs
StatePublished - Dec 16 2011

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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