Neuregulin-induced association of Sos Ras exchange protein with HER2(erbB2)/HER3(erbB3) receptor complexes in Schwann cells through a specific Grb2-HER2(erbB2) interaction

Dev Neurosci. 2001;23(1):25-30. doi: 10.1159/000048693.

Abstract

Neuregulins are members of the epidermal growth factor family of related ligands that exert pleotropic effects during development on the Schwann cell lineage. The receptor complex activated by neuregulin in Schwann cells consists of HER2 (erbB2) and HER3 (erbB3). The intracellular signaling events that follow activation of the HER2/HER3 receptor complex in primary cells, and in particular in Schwann cells, are poorly understood. We have found that neuregulin induces the rapid association of the guanine nucleotide exchange factor SOS with the HER2/HER3 receptor complex. The association of SOS with the HER2/HER3 receptor complex is preceded by the rapid association of Grb2 with the HER2/HER3 receptor complex. Far Western analysis indicates that Grb2 and SOS bind exclusively to HER2 in the HER2/HER3 receptor complex.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Cells, Cultured
  • GRB2 Adaptor Protein
  • Myelin Sheath / metabolism
  • Nerve Fibers, Myelinated / metabolism
  • Neuregulin-1 / metabolism
  • Neuregulins / metabolism*
  • Proteins / metabolism*
  • Rats
  • Receptor, ErbB-2 / metabolism*
  • Receptor, ErbB-3 / metabolism*
  • SOS1 Protein / metabolism*
  • Schwann Cells / cytology
  • Schwann Cells / metabolism*
  • Sciatic Nerve / cytology
  • Signal Transduction / physiology
  • ras Proteins / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • GRB2 Adaptor Protein
  • Grb2 protein, rat
  • Neuregulin-1
  • Neuregulins
  • Proteins
  • SOS1 Protein
  • Receptor, ErbB-2
  • Receptor, ErbB-3
  • ras Proteins