The Target Sites on EGF Receptor for CBL Its Negative Regulator.
Abstract
Recent studies have provided evidence that the Cbl oncogene acts as a negative regulator of the EGFR, by enhancing the rate of degradation of the activated receptor. I have determined that Cbl is a potent negative regulator of the Src family kinase Fyn. Cbl's effect is mediated, at least in part be enhancing the rate of Fyn protein turnover. A known transforming mutant of Cbl, 7OZ-Cbl is incapable of performing this function. Interestingly, Src family kinases are known to be activated by ErbB family members and to enhance the mitogenic response mediated by this family of kinases. Paradoxically, Src has been shown to enhance the rate of internalization of the activated EGFR, but does not alter its rate of degradation. Thus, Src kinases may be involved in regulating the intracellular trafficking or the subcellular localization of activated EGFR. Cbl-mediated negative regulation of Src kinases would provide a novel mechanism by which Cbl could regulate the activated EGPR, and potentially other ErbB family members.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 1999
- Accession Number
- ADA367438
Entities
People
- Christopher E. Andoniou
Organizations
- Brigham and Women's Hospital