title: 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.
authors.affiliation: Program in Molecular Biology and Genetics, Karmanos Cancer Institute, Department of Oncology, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: Dong-Jun
authors.initials: DJ
authors.lastname: Peng
authors.forename: Jun-Ying
authors.initials: JY
authors.lastname: Zhou
authors.forename: Gen Sheng
authors.initials: GS
authors.lastname: Wu
mesh_terms: D020134:Catalytic Domain; D045744:Cell Line, Tumor; D054637:Dual-Specificity Phosphatases / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000235:genetics / Q000378:metabolism*; D008934:Mitogens / Q000494:pharmacology; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D008934:Mitogens; D048049:Extracellular Signal-Regulated MAP Kinases; D054639:Mitogen-Activated Protein Kinase Phosphatases; C490583:DUSP4 protein, human; D054637:Dual-Specificity Phosphatases; D046988:Proteasome Endopeptidase Complex