| First Author | Jirmanova L | Year | 2009 |
| Journal | Blood | Volume | 113 |
| Issue | 10 | Pages | 2229-37 |
| PubMed ID | 19011223 | Mgi Jnum | J:146088 |
| Mgi Id | MGI:3836677 | Doi | 10.1182/blood-2008-04-153304 |
| Citation | Jirmanova L, et al. (2009) Genetic disruption of p38alpha Tyr323 phosphorylation prevents T-cell receptor-mediated p38alpha activation and impairs interferon-gamma production. Blood 113(10):2229-37 |
| abstractText | T cells possess a p38 activation alternative pathway in which stimulation via the antigen receptor (T-cell receptor [TCR]) induces phosphorylation of p38alpha and beta on Tyr323. To assess the contribution of this pathway to normal T-cell function, we generated p38alpha knockin mice in which Tyr323 was replaced with Phe (p38alpha(Y323F)). TCR-mediated stimulation failed to activate p38alpha(Y323F) as measured by phosphorylation of the Thr-Glu-Tyr activation motif and p38alpha catalytic activity. Cell-cycle entry was delayed in TCR-stimulated p38alpha(Y323F) T cells, which also produced less interferon (IFN)-gamma than wild-type T cells in response to TCR-mediated but not TCR-independent stimuli. p38alpha(Y323F) mice immunized with T-helper 1 (Th1)-inducing antigens generated normal Th1 effector cells, but these cells produced less IFN-gamma than wild-type cells when stimulated through the TCR. Thus, the Tyr323-dependent pathway and not the classic mitogen-activated protein (MAP) kinase cascade is the physiologic means of p38alpha activation through the TCR and is necessary for normal Th1 function but not Th1 generation. |
