The Cbl family of signal transduction molecules
- PMID: 9622055
- DOI: 10.1615/critrevoncog.v8.i4.50
The Cbl family of signal transduction molecules
Abstract
This review summarizes the current knowledge about the structure, expression, and signaling function of Cbl. A mutant Cbl form (v-Cbl) was first identified as the product of the Cas-NS-1 murine retrovirus that induces lymphomas and leukemias. Two members of the Cbl family have since been defined in mammals (c-Cbl and Cbl-b), one in C. elegans (Sli-1) and one in Drosophila (D-Cbl). There is high conservation between Cbl species in the amino-terminal region that contains a putative phosphotyrosine binding domain and a Ring finger motif. In the carboxy-terminal region, mammalian Cbl forms share a proline-rich stretch, conserved tyrosine residues, and a leucine zipper. Cbl participates in signaling by receptor protein tyrosine kinases, as well as antigen and cytokine receptors that signal via associated cytoplasmic protein tyrosine kinases. Cbl is recruited to the tyrosine kinase module of these receptors and tyrosine phosphorylated after cellular activation. It functions as a scaffold protein and associates with SH2 and SH3 domain containing molecules, including the Crk adaptor family and Vav. By analogy with the C. elegans homologue Sli-1, Cbl is proposed to be a negative regulator of receptor tyrosine kinase signaling. After deletion mutation in a region close to the Ring finger, c-Cbl becomes oncogenic. Such mutations are suggested to result in a structural alteration, allowing oncogenic mutants to displace wild-type c-Cbl from the receptor complex and to abrogate its negative regulatory function.
Similar articles
-
The protein product of the c-cbl oncogene rapidly complexes with the EGF receptor and is tyrosine phosphorylated following EGF stimulation.Oncogene. 1995 Oct 19;11(8):1561-7. Oncogene. 1995. PMID: 7478580
-
Cbl-b, a member of the Sli-1/c-Cbl protein family, inhibits Vav-mediated c-Jun N-terminal kinase activation.Oncogene. 1997 Nov 20;15(21):2511-20. doi: 10.1038/sj.onc.1201430. Oncogene. 1997. PMID: 9399639
-
The Cbl protooncogene product: from an enigmatic oncogene to center stage of signal transduction.Crit Rev Oncog. 1997;8(2-3):189-218. doi: 10.1615/critrevoncog.v8.i2-3.30. Crit Rev Oncog. 1997. PMID: 9570294 Review.
-
Phosphotyrosine binding domain-dependent upregulation of the platelet-derived growth factor receptor alpha signaling cascade by transforming mutants of Cbl: implications for Cbl's function and oncogenicity.Mol Cell Biol. 1997 Aug;17(8):4597-610. doi: 10.1128/MCB.17.8.4597. Mol Cell Biol. 1997. PMID: 9234717 Free PMC article.
-
The c-Cbl oncoprotein.Int J Biochem Cell Biol. 1998 Apr;30(4):439-44. doi: 10.1016/s1357-2725(97)00075-7. Int J Biochem Cell Biol. 1998. PMID: 9675877 Review.
Cited by
-
c-Cbl: An Important Regulator and a Target in Angiogenesis and Tumorigenesis.Cells. 2019 May 23;8(5):498. doi: 10.3390/cells8050498. Cells. 2019. PMID: 31126146 Free PMC article. Review.
-
Ataxin-2 modulates the levels of Grb2 and SRC but not ras signaling.J Mol Neurosci. 2013 Sep;51(1):68-81. doi: 10.1007/s12031-012-9949-4. Epub 2013 Jan 19. J Mol Neurosci. 2013. PMID: 23335000 Free PMC article.
-
Hydrogen sulfide treatment promotes glucose uptake by increasing insulin receptor sensitivity and ameliorates kidney lesions in type 2 diabetes.Antioxid Redox Signal. 2013 Jul 1;19(1):5-23. doi: 10.1089/ars.2012.5024. Epub 2013 Feb 14. Antioxid Redox Signal. 2013. PMID: 23293908 Free PMC article.
-
Shear Stress Regulates the Flk-1/Cbl/PI3K/NF-κB Pathway Via Actin and Tyrosine Kinases.Cell Mol Bioeng. 2009 Sep 1;2(3):341-350. doi: 10.1007/s12195-009-0069-3. Cell Mol Bioeng. 2009. PMID: 20011623 Free PMC article.
-
Novel c-CBL and CBL-b ubiquitin ligase mutations in human acute myeloid leukemia.Blood. 2007 Aug 1;110(3):1022-4. doi: 10.1182/blood-2006-12-061176. Epub 2007 May 2. Blood. 2007. PMID: 17475912 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Other Literature Sources
Molecular Biology Databases
Miscellaneous