Role of Rab5 in EGF receptor-mediated signal transduction

Authors: M. A. Barbieri¹; Sebastian Fernandez-Pol¹; Christine Hunker¹; Bruce H. Horazdovsky²; Philip D. Stahl¹

Source: European Journal of Cell Biology, Volume 83, Number 6, July 2004 , pp. 305-314(10)

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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 : Delta

, 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.

Document Type: Research article

DOI: http://dx.doi.org/10.1078/0171-9335-00381

Affiliations: 1: Department of Cell Biology and Physiology, Washington University, School of Medicine, St. Louis, Missouri 63110, USA 2: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA

Publication date: 2004-07-01