Phospho-c-Cbl (Tyr774) rabbit mAb Antibody

The c-Cbl (Casitas B-lineage Lymphoma) proto-oncogene is a ubiquitously expressed cytoplasmic adaptor protein that contains multiple functional domains, including an amino-terminal tyrosine kinase-binding (TKB) domain, a RING finger motif, and a proline-rich region. The TKB recognizes phosphorylated tyrosines on activated receptor tyrosine kinases (RTKs) and on other nonreceptor tyrosine kinases, while the RING finger motif recruits ubiquitin-conjugating enzymes. These two domains are primarily responsible for the ubiquitin ligase activity of c-Cbl and downregulation of RTKs (1) . The proline-rich region contains 14-3-3 protein-binding and SH3 domain-binding motifs. c-Cbl is phosphorylated at Y700, Y731, and Y774 by Syk- and Src-family kinases after the stimulation of some integrins and a wide variety of receptors for immunoglobulins, antigens, hormones, growth factors, and cytokines. Phosphorylated Y774 interacts with the SH2 domain of Crk (1,2) . The c-Cbl adapter protein is expressed in the cytoplasm in all tissues, with especially high levels of expression in hematopoietic cells (3,4) . Through its many functional sites, c-Cbl plays key roles in the positive and negative regulation of vital cell functions, including T Cell Receptor-mediated cellular immune responses. In human cancer tissues, c-Cbl is frequently tyrosine-phosphorylated in a tumor-specific manner (5) .