Grb2 interacts with SGEF and antagonizes the ability of SGEF to enhance EGF-induced ERK1/2 activation

Mol Cell Biochem. 2014 Apr;389(1-2):239-47. doi: 10.1007/s11010-013-1945-7. Epub 2014 Jan 8.

Abstract

Previously, we demonstrated that SGEF enhances EGFR stability; however, SGEF-mediated downstream signaling of EGFR is not well understood. Here, we show that SGEF enhances EGF-induced ERK1/2 activation independent of its guanine nucleotide exchange (GEF) activity. We further show that SGEF interacts with Grb2, a critical downstream transducer of EGFR. Surprisingly, we found that interaction of Grb2 to SGEF antagonizes the ability of SGEF to enhance EGF-induced ERK1/2 activation. Taken together, this study reports a novel function of SGEF that excludes GEF and also provides important insights into the complex role of Grb2 in EGFR signal transduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Epidermal Growth Factor / metabolism*
  • GRB2 Adaptor Protein / metabolism*
  • Guanine Nucleotide Exchange Factors / metabolism*
  • HEK293 Cells
  • Humans
  • MAP Kinase Signaling System / physiology*
  • Signal Transduction / physiology

Substances

  • ARHGEF26 protein, human
  • GRB2 Adaptor Protein
  • GRB2 protein, human
  • Guanine Nucleotide Exchange Factors
  • Epidermal Growth Factor