Overexpression of cellular Src in fibroblasts enhances endocytic internalization of epidermal growth factor receptor

J Biol Chem. 1997 Nov 28;272(48):30185-90. doi: 10.1074/jbc.272.48.30185.

Abstract

Previous studies have demonstrated a requirement for the nonreceptor tyrosine kinase, cellular Src (c-Src), in epidermal growth factor (EGF)-induced mitogenesis and a synergistic interaction between c-Src and EGF receptor (EGFR) in tumorigenesis. Although endocytic internalization of EGFR may be thought to attenuate EGF-stimulated signaling, recent evidence suggests that signaling through Ras can be amplified by repeated encounters of endosome-localized, receptor. Shc.Grb2.Sos complexes with the plasma membrane, where Ras resides almost exclusively. Based on these reports, we examined EGFR trafficking behavior in a set of single and double c-Src/EGFR C3H10T1/2 overexpressors to determine if c-Src affects basal receptor half-life, ligand-induced internalization, and/or recycling. Our results show that overexpression of c-Src causes no change in EGFR half-life but does produce an increase in the internalization rate constant of EGF.EGFR complexes when the endocytic apparatus is not stoichiometrically saturated; this effect of c-Src on EGFR endocytosis is negligible at high receptor occupancy in cells overexpressing the receptor. In neither case are EGFR recycling rate constants affected by c-Src. These data indicate a functional role for c-Src in receptor internalization, which in turn could alter some aspects of EGFR signaling related to mitogenesis and tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biological Transport
  • Cell Line
  • Endocytosis
  • Epidermal Growth Factor / metabolism
  • ErbB Receptors / metabolism*
  • Mice
  • Proto-Oncogene Proteins pp60(c-src) / metabolism*
  • Recombinant Proteins / metabolism

Substances

  • Recombinant Proteins
  • Epidermal Growth Factor
  • ErbB Receptors
  • Proto-Oncogene Proteins pp60(c-src)