Direct and specific interaction of c-Src with Neu is involved in signaling by the epidermal growth factor receptor

Oncogene. 1995 Jul 20;11(2):271-9.


Transgenic mice expressing either the activated or wild type neu oncogene heritably develop metastatic mammary tumors. Tumor development in this transgenic mouse model correlates with activation of the Neu tyrosine kinase. Recently, we have shown that these Neu-induced mammary tumors possess elevated c-Src tyrosine kinase activity. Here, we demonstrate that c-Src requires tyrosine phosphorylated Neu for its ability to associate with Neu in vivo and this association is likely the result of a direct physical binding of c-Src SH2 domain to the tyrosine phosphorylated Neu. By contrast, the c-Src SH2 domain did not interact directly with tyrosine phosphorylated EGFR. Moreover, in established cell lines expressing elevated levels of EGFR, EGF stimulation results in transphosphorylation of Neu and formation of complexes between c-Src and tyrosine phosphorylated Neu. Taken together, these observations suggest that activation of c-Src by these two closely related EGFR family members results from a direct and specific interaction of c-Src with tyrosine phosphorylated Neu.

Publication types

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

MeSH terms

  • Animals
  • Antibodies
  • Enzyme Activation
  • Epidermal Growth Factor / pharmacology
  • ErbB Receptors / immunology
  • ErbB Receptors / physiology*
  • Genes, src*
  • Immunoblotting
  • Mammary Neoplasms, Animal / drug therapy
  • Mammary Neoplasms, Animal / enzymology
  • Mammary Neoplasms, Animal / pathology
  • Mice
  • Phosphorylation
  • Phosphotyrosine
  • Precipitin Tests
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / immunology
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins / immunology
  • Proto-Oncogene Proteins / physiology*
  • Receptor, ErbB-2*
  • Signal Transduction / physiology*
  • Tumor Cells, Cultured / drug effects
  • Tyrosine / analogs & derivatives
  • Tyrosine / immunology
  • Tyrosine / metabolism


  • Antibodies
  • Proto-Oncogene Proteins
  • epidermal growth factor receptor-neu receptor
  • Phosphotyrosine
  • Tyrosine
  • Epidermal Growth Factor
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Receptor, ErbB-2