The Target Sites on EGF Receptor for Cb1, It's Negative Regulator
Abstract
Activation of tyrosine kinases plays a key role in breast cancer cell proliferation. ErbB receptors and Src-family tyrosine kinases are specifically implicated in breast cancer. Earlier, we showed that Cb1, a negative regulator of EGF receptor (ErbE1), enhances sorting of the activated EGFR into lysosomes as opposed to its recycling to the cell surface. These findings, together with studies implicating Src-family kinases as positive modulators of EGFR signaling, led us to focus on the potential negative regulatory role of Cb1 for Src-family kinases. Work reported here provides multiple lines of evidence that Cb1 functions as a ubiquitin ligase towards Fyn, a prototype Src-family kinase, and that this leads to an enhancement of Fyn degradation. These results support the role of protein degradation as a general mechanism for Cb1-mediated negative regulation of activated tyrosine kinases and provide a second mechanism for its role in attenuating ErbB signals. Future work will explore the role of Cb1-induced negative regulation of Src-family kinases in sorting ErbB receptors into different intracellular compartments. The proposed studies are aimed at defining novel strategies to downregulate proliferative signals in breast cancer cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2001
- Accession Number
- ADA392379
Entities
People
- Amiya Ghosh
- Hamid Band
Organizations
- Brigham and Women's Hospital