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Oncogene. 2005 Nov 17;24(51):7599-607.

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

Author information

1
Department of Medical Sciences, McMaster University, Hamilton, Ontario, Canada.

Abstract

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.

PMID:
16170374
DOI:
10.1038/sj.onc.1208898
[Indexed for MEDLINE]

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