| Description | 906 amino acids; 115 kDa; the evolutionarily conserved amino-terminal region of CBL is composed of three interacting domains: a four-helix bundle (4H), an EF-hand calcium binding domain, and a divergent SH2 domain; the three domains together form an integrated phosphoprotein-recognition module; this aminoterminal region is followed by a central Ring finger with a Cys3HisCys4 motif and a carboxy-terminal region with multiple proline-rich sequences, a putative leucine zipper and several potential tyrosine phosphorylation sites |
| Expression | ubiquitous but predominant in hematopoietic cells |
| Localisation | cytoplasmic; cellular activation induces translocation of CBL to the plasma membrane or cytoskeleton |
| Function | CBL has been shown to have a negative regulatory activity in protein tyrosine kinase-mediated signaling pathways; CBL overexpresion inhibits cell growth resulting from activation of the EGF and PDGF receptors (EGFR, PDGFRa, PDFFRb) and enhances ubiquitination and degradation of these receptors; CBL also negatively regulates the tyrosine phosphorylation of ZAP70 substrates in T cells |
| v-cbl, an oncogene from a dual-recombinant murine retrovirus that induces early B-lineage lymphomas. |
| Langdon WY, Hartley JW, Klinken SP, Ruscetti SK, Morse HC 3rd |
| Proceedings of the National Academy of Sciences of the United States of America. 1989 ; 86 (4) : 1168-1172. |
| PMID 2784003 |
| |
| The sequences of the human and mouse c-cbl proto-oncogenes show v-cbl was generated by a large truncation encompassing a proline-rich domain and a leucine zipper-like motif. |
| Blake TJ, Shapiro M, Morse HC 3rd, Langdon WY |
| Oncogene. 1991 ; 6 (4) : 653-657. |
| PMID 2030914 |
| |
| Association of a chromosome deletion syndrome with a fragile site within the proto-oncogene CBL2. |
| Jones C, Penny L, Mattina T, Yu S, Baker E, Voullaire L, Langdon WY, Sutherland GR, Richards RI, Tunnacliffe A |
| Nature. 1995 ; 376 (6536) : 145-149. |
| PMID 7603564 |
| |
| The coding region of the Bloom syndrome BLM gene and of the CBL proto-oncogene is mutated in genetically unstable sporadic gastrointestinal tumors. |
| Calin G, Herlea V, Barbanti-Brodano G, Negrini M |
| Cancer research. 1998 ; 58 (17) : 3777-3781. |
| PMID 9731483 |
| |
| Cbl: complex formation and functional implications. |
| Liu YC, Altman A |
| Cellular signalling. 1998 ; 10 (6) : 377-385. |
| PMID 9720760 |
| |
| Cbl: complex formation and functional implications. |
| Liu YC, Altman A |
| Cellular signalling. 1998 ; 10 (6) : 377-385. |
| PMID 9720760 |
| |
