| First Author | Hirata Y | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 9 | Pages | 4621-6 |
| PubMed ID | 23547112 | Mgi Jnum | J:195501 |
| Mgi Id | MGI:5484694 | Doi | 10.4049/jimmunol.1202809 |
| Citation | Hirata Y, et al. (2013) TAK1-JNK Axis Mediates Survival Signal through Mcl1 Stabilization in Activated T Cells. J Immunol 190(9):4621-6 |
| abstractText | TAK1, a member of MAPK kinase kinase (MAPKK-K) family, can activate JNK, p38 MAPK, and NF-kappaB signaling pathways. Although targeted gene disruption studies have demonstrated that TAK1 plays a critical role in T cell functions, precise functions of downstream mediators remain elusive. We used the chemical compound LL-Z1640-2, which preferentially suppressed MAPK activation but not NF-kappaB signal downstream of TAK1. LL-Z1640-2 blocked TCR-induced T cell proliferation and activation, confirming that a TAK1-mediated MAPK signal is essential for T cell activation. LL-Z1640-2 induced apoptosis of activated mouse splenic T cells in a caspase- and caspase-activated DNase-dependent manner. TAK1-JNK pathway, which is activated downstream of IL-2R, induced the phosphorylation of antiapoptotic protein Mcl1 in activated T cells, resulting in the stabilization of Mcl1 protein. Our data uncover that among signal transduction pathways downstream of TAK1, JNK mediates a survival program through Mcl1 stabilization downstream of IL-2R in activated T cells and that blockade of TAK1-JNK pathway can eliminate activated T cells by apoptosis. |
