Cbl-b, a member of the Sli-1/c-Cbl protein family, inhibits Vav-mediated c-Jun N-terminal kinase activation.
dc.contributor.author | Bustelo, Xose R | |
dc.contributor.author | Crespo, Piero | |
dc.contributor.author | López Barahona, Mónica | |
dc.contributor.author | Gutkind, J Silvio | |
dc.contributor.author | Barbacid, Mariano | |
dc.date.accessioned | 2024-02-07T11:29:49Z | |
dc.date.available | 2024-02-07T11:29:49Z | |
dc.date.issued | 1997 | |
dc.description.abstract | We have used the yeast two-hybrid system to identify proteins that interact with Vav, a GDP/GTP exchange factor for the Rac-1 GTPase that plays an important role in cell signaling and oncogenic transformation. This experimental approach resulted in the isolation of Cbl-b, a signal transduction molecule highly related to the mammalian c-cbl proto-oncogene product and to the C. elegans Sli-1 protein, a negative regulator of the EGF-receptor-like Let23 protein. The interaction between Vav and Cbl-b requires the entire SH3-SH2-SH3 carboxy-terminal domain of Vav and a long stretch of proline-rich sequences present in the central region of Cbl-b. Stimulation of quiescent rodent fibroblasts with either epidermal or platelet-derived growth factors induces an increased affinity of Vav for Cbl-b and results in the subsequent formation of a Vav-dependent trimeric complex with the ligand-stimulated tyrosine kinase receptors. During this process, Vav, but not Cbl-b, becomes highly phosphorylated on tyrosine residues. Overexpression of Cbl-b inhibits the signal transduction pathway of Vav that leads to the stimulation of c-Jun N-terminal kinase. By contrast, expression of truncated Cbl-b proteins and of missense mutants analogous to those found in inactive Sli-1 proteins have no detectable effect on Vav activity. These results indicate that Vav and Cbl-b act coordinately in the first steps of tyrosine protein kinase receptor-mediated signaling and suggest that members of the Sli-1/Cbl family are also negative regulators of signal transduction in mammalian cells. | spa |
dc.identifier.doi | 10.1038/sj.onc.1201430 | spa |
dc.identifier.issn | 0950-9232 | spa |
dc.identifier.uri | https://hdl.handle.net/10641/3891 | |
dc.language.iso | eng | spa |
dc.publisher | Oncogene | spa |
dc.relation.publisherversion | https://www.nature.com/articles/1201430 | spa |
dc.rights | Atribución-NoComercial-SinDerivadas 3.0 España | * |
dc.rights.accessRights | open access | spa |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.subject | Cbl family | spa |
dc.subject | Tyrosine phosphorylation | spa |
dc.subject | JNK activation | spa |
dc.title | Cbl-b, a member of the Sli-1/c-Cbl protein family, inhibits Vav-mediated c-Jun N-terminal kinase activation. | spa |
dc.type | journal article | spa |
dc.type.hasVersion | SMUR | spa |
dspace.entity.type | Publication | |
relation.isAuthorOfPublication | f84ad2f1-2f78-4bff-b265-12fd8872e8e3 | |
relation.isAuthorOfPublication.latestForDiscovery | f84ad2f1-2f78-4bff-b265-12fd8872e8e3 |
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