| First Author | Cunningham CA | Year | 2013 |
| Journal | Eur J Immunol | Volume | 43 |
| Issue | 12 | Pages | 3361-71 |
| PubMed ID | 23963642 | Mgi Jnum | J:205863 |
| Mgi Id | MGI:5546548 | Doi | 10.1002/eji.201343635 |
| Citation | Cunningham CA, et al. (2013) The POSH/JIP-1 scaffold network regulates TCR-mediated JNK1 signals and effector function in CD8(+) T cells. Eur J Immunol 43(12):3361-71 |
| abstractText | Signals from the T-cell recognition of antigen program effector functions are necessary to clear infections and tumors. The JNK pathway is critically important in regulating this process. In T lymphocytes, JNK1 and JNK2 have distinct functions depending on their maturation state and cell-type. However, the mechanisms that regulate their isoform-specific activity and function are still unclear. Here, we identify plenty of SH3 (POSH) and JNK-interacting protein 1 (JIP-1) as a multiprotein scaffold network for TCR-mediated JNK1 activation in CD8(+) T cells. Disruption of the POSH/JIP-1 complex led to profound defects in the activation of JNK1, as well as deficient activation or induction of the transcription factors c-Jun, T-bet, and Eomesodermin. Furthermore, disruption of the POSH/JIP complex in CD8(+) T cells resulted in impaired proliferation, decreased cytokine expression, and the inability to control tumors. Collectively, these data identify a mechanism for the specific regulation of TCR-dependent JNK1 activation and function that is key for CD8(+) T-cell responses. |
