Post-translational regulation of mitogen-activated protein kinase phosphatase-2 (MKP-2) by ERK

 Abstract

MKP-2 is a member of the dual-specificity phosphatase family that can dephosphorylate and inactivate mitogen-activated protein kinases (MAPKs). Although MKP-2 can be induced by ERK signaling, little is known about the regulation of MKP-2 at the post-translational level. Here we show that MKP-2 is phosphorylated by ERK and that such phosphorylation leads to stabilization of MKP-2 protein. Importantly, we find that MKP-2 can be phosphorylated on Ser386 and Ser391 at its C-terminus. Blockage of ERK activation results in enhanced proteasomal degradation of MKP-2 protein. Moreover, we find that phosphorylation has no effect on MKP-2 phosphatase activity. Taken together, these results illustrate an important post-translational regulation of MKP-2 protein as a feedback mechanism to control ERK activity.

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Pages
4650 - 4655
doi
10.4161/cc.9.23.13957
Type
Report
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Post-translational regulation of mitogen-activated protein kinase phosphatase-2 (MKP-2) by ERK