Role of Rab5 in EGF receptor-mediated signal transduction Article

Barbieri, MA, Fernandez-Pol, S, Hunker, C et al. (2004). Role of Rab5 in EGF receptor-mediated signal transduction . EUROPEAN JOURNAL OF CELL BIOLOGY, 83(6), 305-314. 10.1078/0171-9335-00381

cited authors

  • Barbieri, MA; Fernandez-Pol, S; Hunker, C; Horazdovsky, BH; Stahl, PD


  • Activated epidermal growth factor receptor (EGFR) recruits intracellular proteins that mediate receptor trafficking and signaling. Rab5 and Rin1, a multifunctional protein with a Rab5 guanine nucleotide exchange factor domain, have been shown to regulate EGFR endocytosis (Barbieri et al., 2000; Tall et al., 2001). In this study, we demonstrate that overexpression of both dominant negative Rab5 (Rab5:S34N) and full-length Rin1 selectively block EGF activation of the Raf-Erk1/2 kinase pathway and EGF-stimulated incorporation of [3H]thymidine into DNA without affecting the activity of JN and p38 kinase pathways. Expression of Rab5:S34N and Rin1 also block EGF induction of cyclin D1 transcription. In contrast, expression of Rin1:Δ, a natural splice variant of Rin1 lacking 47 amino acids in the Vps9p domain or Rab5, increase both activation of Raf-Erk1/2- and cyclin D1 transcription in response to EGF. These results indicate that Rab5 and the Raf/Erk signal transduction pathway play essential and selective roles in EGF-induced cell proliferation, and highlight a new function for Rab5 in EGF signaling.

publication date

  • January 1, 2004

published in

Digital Object Identifier (DOI)

start page

  • 305

end page

  • 314


  • 83


  • 6