Overview:

p38alpha (a.k.a. SAPK2A) is a member of the p38 MAPK family, which are activated by various environmental stresses and proinflammatory cytokines (1). The activation of p38 requires its phosphorylation by MAP kinase kinases (MKKs) or by autophosphorylation triggered by the interaction of MAP3K7IP1/TAB1 protein with this kinase (2). The substrates of p38 include the transcriptional regulators ATF2, MEF2C, MAX, the cell cycle regulator CDC25B, and the tumor suppressor p53. Its wide range of targets suggest that p38 has roles in stress related transcription, cell cycle regulation and genotoxic stress response. Like the other MAPKs, p38 is activated by a dual specificity kinase that phosphorylates Thr180 and Tyr182 (3).

References:

1. Han, J. et al: A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science 265: 808-811, 1994.

2. Ge, B. et al: MAPKK-independent activation of p38-alpha mediated by TAB1-dependent autophosphorylation of p38-alpha. Science 295: 1291-1294, 2002.

3. Lin A. et al: Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2. Science 268:286-290, 1995.