| First Author | Shao Y | Year | 2004 |
| Journal | J Biol Chem | Volume | 279 |
| Issue | 42 | Pages | 43646-53 |
| PubMed ID | 15304502 | Mgi Jnum | J:119327 |
| Mgi Id | MGI:3701759 | Doi | 10.1074/jbc.M404082200 |
| Citation | Shao Y, et al. (2004) Differential regulation of the B cell receptor-mediated signaling by the E3 ubiquitin ligase Cbl. J Biol Chem 279(42):43646-53 |
| abstractText | The E3 ubiquitin ligase Cbl has been implicated in intracellular signaling pathways induced by the engagement of the B cell antigen receptor (BCR) as a negative regulator. Here we showed that Cbl deficiency results in a reduction of B cell proliferation. Cbl-/- B cells show impaired tyrosine phosphorylation, reduced Erk activation, and attenuated calcium mobilization in response to BCR engagement. The phosphorylation of Syk and Btk is also down-modulated. Interestingly, Cbl-/- B cells display enhanced BCR-induced phosphorylation of CD19 and its association with phosphatidylinositol 3-kinase. Importantly, Lyn kinase activity is up-regulated in Cbl-/- B cells, which correlates inversely with the Cbl-mediated ubiquitination of Lyn. Because Lyn has both negative and positive roles in B cells, our results suggested that Cbl differentially modulates the BCR-mediated signaling pathways through targeting Lyn ubiquitination, which affects B cell development and activation. |
