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Gene Review

Cbl  -  CG7037 gene product from transcript CG7037-RB

Drosophila melanogaster

Synonyms: CBL, CG7037, CG7043, D-Cbl, D-Cbl L, ...
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High impact information on Cbl

  • In addition, Egfr activity has to be repressed through the activity of D-cbl to ensure the absence of signaling in the ventral most follicle cells [1].
  • In lysates of adult transgenic Drosophila melanogaster, GST-DCbl binds to the tyrosine-phosphorylated 150-kDa torso-DER chimeric receptor [2].
  • Expression of D-Cbl directed by the sevenless enhancer in intact Drosophila compromises severely the development of the R7 photoreceptor neuron [2].
  • Interactions of Drosophila Cbl with epidermal growth factor receptors and role of Cbl in R7 photoreceptor cell development [2].
  • Evidence for direct interaction between Sprouty and Cbl [3].

Biological context of Cbl


Anatomical context of Cbl

  • Cbl protein is shown to be localised to axons of the longitudinal connectives and commissures in the central nervous system [6].
  • Finally, oncogenic mutants of Cbl, when expressed in fibroblasts, upregulate the signaling cascade downstream of the platelet-derived growth factor receptor alpha in a Cbl-PTB domain-dependent manner [7].
  • Both isoforms are maternally expressed but the long isoform of D-cbl is also transiently expressed in the invaginating mesoderm and later is specifically expressed in neurons of the central nervous system (CNS) [6].

Associations of Cbl with chemical compounds

  • Cbl has emerged as a novel signal transducing protein downstream of a number of cell surface receptors coupled to tyrosine kinases [7].
  • There is high conservation between Cbl species in the amino-terminal region that contains a putative phosphotyrosine binding domain and a Ring finger motif [8].
  • Cbl and Sprint both regulate early steps of RTK endocytosis [9].

Regulatory relationships of Cbl


Other interactions of Cbl

  • The corresponding mutation in human Cbl inactivates the PTB domain function and abrogates Cbl-mediated regulation of tyrosine kinase function [11].
  • Cbl proteins associate with many different cell signalling molecules suggesting that they may have functions outside of the RING finger-mediated ubiquitin ligase activity [6].
  • Additionally, both Caenorhabditis elegans and Drosophila Cbl homologs, SLI-1 and D-Cbl, respectively, have been identified as negative regulators of the LET-23/DER receptor tyrosine kinases [7].


  1. D-cbl, a negative regulator of the Egfr pathway, is required for dorsoventral patterning in Drosophila oogenesis. Pai, L.M., Barcelo, G., Schüpbach, T. Cell (2000) [Pubmed]
  2. Interactions of Drosophila Cbl with epidermal growth factor receptors and role of Cbl in R7 photoreceptor cell development. Meisner, H., Daga, A., Buxton, J., Fernández, B., Chawla, A., Banerjee, U., Czech, M.P. Mol. Cell. Biol. (1997) [Pubmed]
  3. Evidence for direct interaction between Sprouty and Cbl. Wong, E.S., Lim, J., Low, B.C., Chen, Q., Guy, G.R. J. Biol. Chem. (2001) [Pubmed]
  4. A Drosophila analogue of v-Cbl is a dominant-negative oncoprotein in vivo. Robertson, H., Hime, G.R., Lada, H., Bowtell, D.D. Oncogene (2000) [Pubmed]
  5. D-Cbl, the Drosophila homologue of the c-Cbl proto-oncogene, interacts with the Drosophila EGF receptor in vivo, despite lacking C-terminal adaptor binding sites. Hime, G.R., Dhungat, M.P., Ng, A., Bowtell, D.D. Oncogene (1997) [Pubmed]
  6. Dynamic expression of alternate splice forms of D-cbl during embryogenesis. Hime, G.R., Abud, H.E., Garner, B., Harris, K.L., Robertson, H. Mech. Dev. (2001) [Pubmed]
  7. The c-Cbl oncoprotein. Lupher, M.L., Andoniou, C.E., Bonita, D., Miyake, S., Band, H. Int. J. Biochem. Cell Biol. (1998) [Pubmed]
  8. The Cbl family of signal transduction molecules. Smit, L., Borst, J. Critical reviews in oncogenesis. (1997) [Pubmed]
  9. Regulators of endocytosis maintain localized receptor tyrosine kinase signaling in guided migration. Jékely, G., Sung, H.H., Luque, C.M., Rørth, P. Dev. Cell (2005) [Pubmed]
  10. Differential effects of Cbl isoforms on Egfr signaling in Drosophila. Pai, L.M., Wang, P.Y., Chen, S.R., Barcelo, G., Chang, W.L., Nilson, L., Schüpbach, T. Mech. Dev. (2006) [Pubmed]
  11. The Cbl protooncogene product: from an enigmatic oncogene to center stage of signal transduction. Miyake, S., Lupher, M.L., Andoniou, C.E., Lill, N.L., Ota, S., Douillard, P., Rao, N., Band, H. Critical reviews in oncogenesis. (1997) [Pubmed]
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