We have updated our privacy policy. If you have any question, contact us at privacy@scicrunch.org. Dismiss and don't show again

Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Cbl-mediated ubiquitinylation and negative regulation of Vav.

The Cbl ubiquitin ligase has emerged as a negative regulator of receptor and non-receptor tyrosine kinases. Cbl is known to associate with the proto-oncogene product Vav, a hematopoietic-restricted Rac guanine nucleotide exchange factor, but the consequences of this interaction remain to be elucidated. Using immortalized T cell lines from Cbl(+/+) and Cbl(-/-) mice, and transfection analyses in 293T cells, we demonstrate that Vav undergoes Cbl-dependent ubiquitinylation under conditions that promote Cbl and Vav phosphorylation. Interaction with Cbl also induced the loss of phosphorylated Vav. In addition, we show that an activated Vav mutant (Vav-Y174F) is more sensitive to Cbl-dependent ubiquitinylation. We demonstrate that the Cbl-dependent ubiquitinylation of Vav requires Cbl/Vav association through phosphorylated Tyr-700 on Cbl, and also requires an intact Cbl RING finger domain. Finally, using transfection analyses in the Jurkat T cell line, we show that Cbl, but not its ubiquitin ligase mutant, can inhibit Vav-dependent signaling. Thus, our findings strongly support the role of Cbl, via its ubiquitin ligase activity, as a negative regulator of activated Vav.

Pubmed ID: 12881521 RIS Download

Mesh terms: Animals | Cell Line | Electrophoresis, Polyacrylamide Gel | Gene Expression Regulation | Humans | Immunoblotting | Jurkat Cells | Luciferases | Mice | Mice, Transgenic | Models, Genetic | Mutation | Oncogene Protein v-cbl | Oncogene Proteins | Phosphorylation | Plasmids | Precipitin Tests | Protein Binding | Protein Structure, Tertiary | Proto-Oncogene Proteins c-vav | Retroviridae Proteins, Oncogenic | Signal Transduction | Time Factors | Transfection | Tyrosine | Ubiquitin | Vanadates

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NCI NIH HHS, Id: CA70195
  • Agency: NCI NIH HHS, Id: CA75075
  • Agency: NCI NIH HHS, Id: CA76118
  • Agency: NCI NIH HHS, Id: CA81076
  • Agency: NCI NIH HHS, Id: CA87986
  • Agency: NCI NIH HHS, Id: CA99163
  • Agency: NCI NIH HHS, Id: CA99900

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.