Regulation of FAK Signaling in Mammary Epithelial Cells by Cbl Proto-Oncogene Product
Abstract
Proliferation and differentiation of normal breast epithelial cells are regulated by activation of the cellular tyrosine kinase machinery upon coordinated cellular stimulation through growth factor receptor tyrosine kinases and extra-cellular matrix receptor-induced activation of focal adhesion kinase FAK. This proposal is designed to investigate a novel hypothesis that Cbl provides, which has become established as a negative regulator of growth factor receptors, attenuates FAK-dependent growth signals in mammary epithelial cells. Given the recent findings that Cbl functions as ubiquitin ligase towards tyrosine kinases, we have been examining the possibility that Cbl regulates FAK signaling by targeting it for degradation directly and/or by targeting Src-family kinases that function as upstream activators of FAK. The work reported here describes FAK mutants that appear to be unable to interact with Cbl tyrosine kinase-binding domain and their ability to alter actin cytoskeleton. Together with the demonstration of Src-family degradation and negative regulation by Cbl, the present studies establish FAK as a target of Cbl. Further studies based on these novel findings are likely to provide important insights into the regulation of proliferation signals in breast cancer cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2003
- Accession Number
- ADA418422
Entities
People
- Amiya Ghosh
- Hamid Band
- Stephen Donoghue
Organizations
- Brigham and Women's Hospital