The c-Src tyrosine kinase associates with the catalytic domain of ErbB-2: implications for ErbB-2 mediated signaling and transformation

Oncogene. 2005 Nov 17;24(51):7599-607. doi: 10.1038/sj.onc.1208898.


c-Src associates with and is activated by the ErbB-2 receptor tyrosine kinase, but is unable to bind the EGFR. Although c-Src has been found to interact directly and specifically with the ErbB-2 receptor, the significance of this interaction is unclear. Using both chimeric receptor and site-directed mutagenesis approaches, the region of interaction of c-Src on ErbB-2 was identified. Significantly, EGFR could be converted into a receptor capable of binding c-Src by replacement of a catalytic domain of ErbB-2. We further demonstrated that MDCK cells that express mutant EGFR that are competent in c-Src recruitment lose epithelial polarity in organoid cultures, whereas cells overexpressing the wild-type EGFR retain a polarized phenotype. ErbB-2-dependent activation of c-Src results in disruption of epithelial cell-cell contacts leading to cell dispersal that correlates with the re-localization of phospho-MAPK to focal adhesions. Taken together, these observations suggest that recruitment of c-Src to these closely related EGFR family members plays a critical role in modulating cell polarity.

Publication types

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

MeSH terms

  • Animals
  • Binding Sites
  • CSK Tyrosine-Protein Kinase
  • Catalytic Domain
  • Cell Differentiation
  • Cell Line
  • Cell Polarity / physiology*
  • Cell Transformation, Neoplastic*
  • Dogs
  • ErbB Receptors / genetics*
  • ErbB Receptors / physiology
  • Focal Adhesions
  • Humans
  • Kidney / cytology
  • Mutagenesis, Site-Directed
  • Mutation
  • Protein-Tyrosine Kinases / metabolism*
  • Rats
  • Receptor, ErbB-2 / physiology*
  • Recombinant Fusion Proteins
  • Signal Transduction
  • src-Family Kinases


  • Recombinant Fusion Proteins
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Receptor, ErbB-2
  • CSK Tyrosine-Protein Kinase
  • src-Family Kinases
  • CSK protein, human