Figure 1.

The p38 mitogen-activated protein kinase (MAPK) signaling cascade in T cells. Activation of p38 MAPK requires dual phosphorylation at Thr180 (T180) and Tyr182 (Y182) and can be mediated by two different pathways in T cells. The classical pathway is formed by a conserved MAPK module and is activated by the T cell receptor (TCR), CD28, or the IL-12/IL-18 receptors through growth arrest and DNA damage-inducible genes (GADD)45α or GADD45β. The alternative pathway is activated by the TCR and induces the phosphorylation of p38 MAPK at Tyr323 (Y323) and subsequent autophosphorylation of p38 MAPK at Thr180 and Tyr182 that can be blocked by GADD45α. MKK, MAPK kinase; ζ₂, zeta chain homodimer.