MAPKK-independent activation of p38alpha mediated by TAB1-dependent autophosphorylation of p38alpha.

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Citation

Ge B, Gram H, Di Padova F, Huang B, New L, Ulevitch RJ, Luo Y, Han J

MAPKK-independent activation of p38alpha mediated by TAB1-dependent autophosphorylation of p38alpha.

Science. 2002 Feb 15;295(5558):1291-4.

PubMed ID
11847341 [ View in PubMed
]
Abstract

Phosphorylation of mitogen-activated protein kinases (MAPKs) on specific tyrosine and threonine sites by MAP kinase kinases (MAPKKs) is thought to be the sole activation mechanism. Here, we report an unexpected activation mechanism for p38alpha MAPK that does not involve the prototypic kinase cascade. Rather it depends on interaction of p38alpha with TAB1 [transforming growth factor-beta-activated protein kinase 1 (TAK1)-binding protein 1] leading to autophosphorylation and activation of p38alpha. We detected formation of a TRAF6-TAB1-p38alpha complex and showed stimulus-specific TAB1-dependent and TAB1-independent p38alpha activation. These findings suggest that alternative activation pathways contribute to the biological responses of p38alpha to various stimuli.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Mitogen-activated protein kinase 14Q16539Details