Cell Signaling by a Novel SH2 Domain Protein That is Overexpressed with HER2 in Breast Cancer
Final rept. 1 Dec 1994-30 Nov 1999
NEW YORK UNIV MEDICAL CENTER NY
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The goal of this project was to determine the role of the Src homology 2 domain protein, Grb7, in receptor tyrosine kinase signal transduction. Grb7 is overexpressed in approximately twenty percent of breast cancers coordinately with the HER2 receptor tyrosine kinase. Grb7 binds to HER2 but the role of Grb7 in HER2 signaling is unknown. We have been unable to detect a phenotype in breast or kidney epithelial cells that overexpress Grb7. Grb7 deficient mice have also been generated as another approach to analyze Grb7 function. No obvious phenotypic abnormality has been observed in these Grb7 deficient mice including no deficits in development or fertility. Thus despite performing studies where Grb7 is overexpressed or Grb7 expression is eliminated, the tme biologic function of this protein remains elusive. In a separate set of studies we have analyzed another HER2 binding protein called Shc. We have demonstrated a crucial role for the Shc phosphotyrosine binding domain in Shc mediated cell transformation.
- Medicine and Medical Research