Cloning and characterization of a novel adaptor protein, CIN85, that interacts with c-Cbl

The c-Cbl protooncogene product is a prominent substrate of protein tyrosin e kinases and is rapidly tyrosine-phosphorylated upon stimulation of a wide variety of cell-surface receptors, We have identified a novel c-Cbl-intera cting protein termed CIN85 with a molecular mass of 85 kDa which shows simi larity to adaptor proteins, CMS and CD2AP, CIN85 mRNA is expressed ubiquito usly in normal human tissues and cancer cell lines analyzed. CIN85 was basa lly associated with c-Cbl. For interaction of CIN85 with c-Cbl, the second SH3 domain of CIN85 was shown to serve as a central player. The CIN85-c-Cbl association was enhanced shortly after stimulation of 293 cells with epide rmal growth factor (EGF) and gradually diminished to a basal level, which c orrelated with a tyrosine phosphorylation level of c-Cbl. Our results sugge st that CIN85 may play a specific role in the EGF receptor-mediated signali ng cascade via its interaction with c-Cbl. (C) 2000 Academic Press.