Other
11 Authors
- Liang Y,
- Yang L,
- Li Z,
- Lipkowitz S,
- Langdon WY,
- Ying H,
- Zhao Y,
- Zhang J,
- Guo H,
- Qiao G,
- Penninger JM
| First Author | Guo H | Year | 2012 |
| Journal | Cell Rep | Volume | 1 |
| Issue | 5 | Pages | 472-82 |
| PubMed ID | 22763434 | Mgi Jnum | J:196025 |
| Mgi Id | MGI:5486416 | Doi | 10.1016/j.celrep.2012.04.008 |
| Citation | Guo H, et al. (2012) E3 ubiquitin ligase Cbl-b regulates Pten via Nedd4 in T cells independently of its ubiquitin ligase activity. Cell Rep 1(5):472-82 |
| abstractText | E3 ubiquitin ligase Cbl-b plays a crucial role in T cell activation and tolerance induction. However, the molecular mechanism by which Cbl-b inhibits T cell activation remains unclear. Here, we report that Cbl-b does not inhibit PI3K but rather suppresses TCR/CD28-induced inactivation of Pten. The elevated Akt activity in Cbl-b(-/-) T cells is therefore due to heightened Pten inactivation. Suppression of Pten inactivation in T cells by Cbl-b is achieved by impeding the association of Pten with Nedd4, which targets Pten K13 for K63-linked polyubiquitination. Consistent with this finding, introducing Nedd4 deficiency into Cbl-b(-/-) mice abrogates hyper-T cell responses caused by the loss of Cbl-b. Hence, our data demonstrate that Cbl-b inhibits T cell activation by suppressing Pten inactivation independently of its ubiquitin ligase activity. |
