Heregulin and HER2 signaling selectively activates c-Src phosphorylation at tyrosine 215

FEBS Lett. 2003 May 22;543(1-3):76-80. doi: 10.1016/s0014-5793(03)00404-6.


To elucidate the molecular mechanisms by which human epidermal growth factor receptor/heregulin (HER2/HRG) influence the migratory potential of breast cancer cells, we have used phospho-specific antibodies against c-Src kinase and focal adhesion kinase (FAK). This study establishes that HER2/HRG signaling selectively upregulates Tyr phosphorylation of c-Src at Tyr-215 located within the SH2 domain, increases c-Src kinase activity and selectively upregulates Tyr phosphorylation of FAK at Tyr-861. HER2-overexpressing tumors showed increased levels of c-Src phosphorylation at Tyr-215. These findings suggest that HER2/HRG influence metastasis of breast cancer cells through a novel signaling pathway involving phosphorylation of FAK tyrosine 861 via activation of c-Src tyrosine 215.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Animals
  • Breast Neoplasms / metabolism
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Humans
  • Mice
  • Neuregulin-1 / pharmacology*
  • Phosphorylation
  • Protein-Tyrosine Kinases / chemistry
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins pp60(c-src) / chemistry*
  • Proto-Oncogene Proteins pp60(c-src) / metabolism*
  • Receptor, ErbB-2 / metabolism*
  • Signal Transduction
  • Tumor Cells, Cultured
  • Tyrosine / metabolism*
  • Up-Regulation


  • Neuregulin-1
  • Tyrosine
  • Protein-Tyrosine Kinases
  • Receptor, ErbB-2
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • PTK2 protein, human
  • Proto-Oncogene Proteins pp60(c-src)
  • Ptk2 protein, mouse