The mechanism and function of mitogen-activated protein kinase activation by ARF1

Fuguo Zhou, Chunmin Dong, Jason E. Davis, William H. Wu, Kristen Surrao, Guangyu Wu

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Mitogen-activated protein kinases (MAPK) can be activated by a number of biochemical pathways through distinct signaling molecules. We have recently revealed a novel function for the Ras-like small GTPase ADP-ribosylation factor 1 (ARF1) in mediating the activation of Raf1-MEK-ERK1/2 pathway by G protein-coupled receptors [Dong C, Li C and Wu G (2011) J Biol Chem 286, 43,361-43,369]. Here, we have further defined the underlying mechanism and the possible function of ARF1-mediated MAPK pathway. We demonstrated that the blockage of ARF1 activation and the disruption of ARF1 localization to the Golgi by mutating Thr48, a highly conserved residue involved in the exchange of GDP for GTP, and the myristoylation site Gly2 abolished ARF1's ability to activate ERK1/2. In addition, treatment with Golgi structure disrupting agents markedly attenuated ARF1-mediated ERK1/2 activation. Furthermore, ARF1 significantly promoted cell proliferation. More interestingly, ARF1 activated 90. kDa ribosomal S6 kinase 1 (RSK1) without influencing Elk-1 activation and ERK2 translocation to the nuclei. These data demonstrate that, once activated, ARF1 activates the MAPK pathway likely using the Golgi as a main platform, which in turn activates the cytoplasmic RSK1, leading to cell proliferation.

Original languageEnglish (US)
Pages (from-to)2035-2044
Number of pages10
JournalCellular Signalling
Issue number10
StatePublished - Oct 1 2015


  • ARF1
  • Cell proliferation
  • ERK1/2
  • G protein
  • G protein-coupled receptor
  • MAPK
  • RSK1

ASJC Scopus subject areas

  • Cell Biology


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