MAPKK-independent activation of p38α mediated by TAB1-dependent autophosphorylation of p38α
MAPKK-independent activation of p38α mediated by TAB1-dependent autophosphorylation of p38α
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DOI：
10.1126/science.1067289
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发表时间：
2002-02-15
期刊：
影响因子：
56.9
通讯作者：
Han, JH
中科院分区：
文献类型：
--
作者：
Ge, BX;Gram, H;Han, JH
丝裂原活化蛋白激酶(MAPKs)在特定的酪氨酸和苏氨酸位点上被认为是唯一的激活机制。在这里，我们报告了一种意想不到的p38pha MAPK激活机制，它不涉及原型激酶级联。相反，它依赖于p38α与TAB1[转化生长因子-β激活蛋白激酶1(TAK1)结合蛋白1]的相互作用，导致p38α的自动磷酸化和激活。我们检测到TRAF6-TAB1-P38α复合体的形成，并显示出刺激特异性的TAB1依赖和TAB1非依赖的P38Alpha激活。这些发现表明，不同的激活途径参与了p38α对不同刺激的生物学反应。
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.