The cbl oncogene was first identified as part of a transforming retrovirus which induces mouse pre-B and pro-B cell lymphomas. As an adaptor protein for receptor protein-tyrosine kinases, it positively regulates receptor protein-tyrosine kinase ubiquitination in a manner dependent upon its variant SH2 and RING finger domains. Ubiquitination of receptor protein-tyrosine kinases terminates signaling by marking active receptors for degradation. [provided by RefSeq, Jul 2008]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications.
Function: Participates in signal transduction in hematopoietic cells. Adapter protein that functions as a negative regulator of many signaling pathways that start from receptors at the cell surface. Acts as an E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Recognizes activated receptor tyrosine kinases, including PDGFA, EGF and CSF1, and terminates signaling. Essential for osteoclastic bone resorption. The Tyr-731 phosphorylated form induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function.