Regulation of FAK Signaling in Mammary Epithelial Cells by Cb1 Protooncogene 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. For this purpose, the Cbl interaction sites on FAK will be determined and the impact of mutations in these sites on the ability of FAK to mediate growth signals will be investigated. Given the recent findings that Cbl functions as ubiquitin ligase towards tyrosine kinases, we are examining the possibility that Cbl regulates FAK signaling by targeting it for degradation. The work reported here describes FAK mutants that appear to be unable to interact with Cbl tyrosine kinase-binding domain. Together with the generation of mutant forms of Cbl that are unable to mediate ubiquitination, these studies will directly establish if FAK is a target of Cbl. The present studies, thus, aim to define novel strategies to down-regulate proliferation signals in breast cancer cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2001
- Accession Number
- ADA392426
Entities
People
- Hamid Band
- Patrice Douillard
Organizations
- Brigham and Women's Hospital