Independent regulation of Rap1 and mitogen-activated protein kinase by the α chain of Go

Francesca Bernasconi, Antonio Malgaroli, Lucia Vallar

Research output: Contribution to journalArticlepeer-review

Abstract

Receptors coupled to Gi/o proteins stimulate the mitogen-activated protein kinase (MAPK) cascade. The intracellular pathways linking the α chains of these G proteins to MAPK activation are not completely understood. One of the signaling molecules which has been suggested to act downstream of Gαi/o is the small G protein Rap1. We investigated the role of Rap1 in MAPK stimulation by Gαo in Chinese hamster ovary (CHO) cells. Our previous results have shown that in this cell system activated Gαo strongly potentiates the MAPK response to the epidermal growth factor (EGF) receptor. Rap1 regulation was examined in cells transfected with Rap1 and wild-type Gαo or the activated mutant Gαo-Q205L. Immunocytochemical analysis detected both Rap1 and the Gαo subunit at the plasma membrane as well as on perinuclear cytoplasmic vesicles. Expression of wild-type Gαo had no significant effect on the levels of activated Rap1. In contrast, Gαo-Q205L virtually abolished the activation of Rap1 induced by EGF. Further experiments showed that MAPK stimulation by EGF was greatly inhibited by expression of activated Rap1, suggesting that Rap1 inhibition could mediate the effect of Gαo on the MAPK cascade. However, Gαo-Q205L efficiently inhibited the activation of Rap1 induced by fibroblast growth factor (FGF). We have previously found that the ability of FGF to activate MAPK is not modified by Gαo. In addition, expression of the GAP protein RAP1GAPII blocked Rap1 activation without affecting EGF- or FGF-dependent MAPK stimulation. These findings provide evidence for independent regulation of Rap1 and MAPK by the G oα chain.

Original languageEnglish
Pages (from-to)180-189
Number of pages10
JournalNeuroSignals
Volume15
Issue number4
DOIs
Publication statusPublished - Jun 2007

Keywords

  • Cell growth
  • Cell type differentiation
  • G proteins
  • G
  • Mitogen-activated protein kinase
  • Rap1

ASJC Scopus subject areas

  • Neuroscience(all)

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