Activating p38 MAPK - New tricks for an old kinase
Activating p38 MAPK - New tricks for an old kinase
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DOI：
10.4161/cc.4.9.2043
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发表时间：
2005-09-01
期刊：
影响因子：
4.3
通讯作者：
Ashwell, JD
中科院分区：
文献类型：
--
作者：
Mittelstadt, PR;Salvador, JSM;Ashwell, JD
Mitogen-activated protein kinases (MAPKs) participate in signaling initiated by a wide variety of extracellular stimuli. MAPKs are most commonly activated by a series of phosphorylation events in which one kinase phosphorylates another, the "MAPK cascade". The cascade concludes with the dual phosphorylation of MAPKs on a conserved Thr-X-Tyr motif. In the case of the p38 MAPK, an exception to this paradigm has been found when signaling via the T cell antigen receptor (TCR). Rather than trigger the MAPK cascade, TCR-mediated stimulation activates proximal tyrosine kinases, which results in the phosphorylation of p38 on a noncanonical activating residue, Tyr-323. This phosphorylation activates p38 to phosphorylate third party substrates as well as its own Thr-Gyl-Tyr motif. Here we discuss the structural and functional implications of this alternative p38 activation pathway, which may provide a new target for tissue-specific pharmacologic inhibition.
