Tyrosine Phosphorylation of Cbl upon Epidermal Growth Factor (EGF) Stimulation and Its Association with EGF Receptor and Downstream Signaling Proteins

Toru Fukazawa, Sachiko Miyake, Vimla Band, Hamid Band
1996 Journal of Biological Chemistry  
We and others have shown that Cbl, the protein product of the c-cbl proto-oncogene, is an early target of tyrosine phosphorylation upon stimulation through the immune cell surface receptors, which signal through noncovalently associated cytoplasmic tyrosine kinases. Using human mammary epithelial cells that express a natural epidermal growth factor (EGF) receptor and require EGF as an essential growth factor, we demonstrate here that Cbl is a prominent target of tyrosine phosphorylation upon
more » ... mulation through the EGF receptor tyrosine kinase. Phosphorylation of Cbl was EGF dose-dependent, rapid (detectable as early as 5 s and maximal by 2 min), and relatively sustained (detectable even after 1 h). Co-immunoprecipitation studies demonstrated that Cbl became associated with the EGF receptor in an EGF-dependent manner. Cbl was basally associated with the adaptor protein growth factor receptorbinding protein 2 (Grb2), and this interaction was further enhanced by EGF stimulation; however, the interaction was entirely mediated via the Grb2
doi:10.1074/jbc.271.24.14554 pmid:8662998 fatcat:uji7am2gxbc4heeilewba4mg4q