Activating p38 MAPK: New Tricks for an Old Kinase

 Abstract

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-X-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.

Full Text Options
Article
Metrics
 Share
 Info
Pages
1189 - 1192
doi
10.4161/cc.4.9.2043
Type
Perspectives
 Metrics
 Cite This Article
 Permissions
 Permissions
 Reprints
Activating p38 MAPK: New Tricks for an Old Kinase