| First Author | Salvador JM | Year | 2005 |
| Journal | Nat Immunol | Volume | 6 |
| Issue | 4 | Pages | 396-402 |
| PubMed ID | 15735649 | Mgi Jnum | J:97608 |
| Mgi Id | MGI:3575938 | Doi | 10.1038/ni1176 |
| Citation | Salvador JM, et al. (2005) The autoimmune suppressor Gadd45alpha inhibits the T cell alternative p38 activation pathway. Nat Immunol 6(4):396-402 |
| abstractText | The p38 MAP kinase (MAPK) is phosphorylated and activated by upstream MAPK kinases. T cells have an alternative pathway in which T cell receptor-activated tyrosine kinase Zap70 phosphorylates p38 on Tyr323. Mice lacking Gadd45alpha, a small p38-binding molecule, develop a lupus-like autoimmune disease. Here we show that resting T cells but not B cells from Gadd45a(-/-) mice had spontaneously increased p38 activity in the absence of 'upstream' MAPK kinase activation. The p38 from resting Gadd45a(-/-) T cells was spontaneously phosphorylated on Tyr323, and its activity was specifically inhibited by recombinant Gadd45alpha in vitro. Thus, constitutive activation of T cell p38 through the alternative pathway is prevented by Gadd45alpha, the absence of which results in p38 activation, T cell hyperproliferation and autoimmunity. |
