Role of Rab5 in EGF receptor-mediated signal transduction

M. Alejandro Barbieri, Sebastian Fernandez-Pol, Christine Hunker, Bruce H. Horazdovsky, Philip D. Stahl

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)305-314
Number of pages10
JournalEuropean Journal of Cell Biology
Volume83
Issue number6
DOIs
StatePublished - Jul 2004

Keywords

  • EGF
  • Rab5
  • Rin1
  • Signal transduction

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

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