Phosphorylation of Protein Phosphatase 2Cζ by c-Jun NH2-Terminal Kinase at Ser92 Attenuates Its Phosphatase Activity Export

@article{citeulike:2894309, abstract = {Abstract: The protein phosphatase 2C (PP2C) family represents one of the four major protein Ser/Thr phosphatase activities in mammalian cells and contains at least 13 distinct gene products. Although PP2C family members regulate a variety of cellular functions, mechanisms of regulation of their activities are largely unknown. Here, we show that PP2C{\P}, a PP2C family member that is enriched in testicular germ cells, is phosphorylated by c-Jun NH2-terminal kinase (JNK) but not by p38 in vitro. Mass spectrometry and mutational analyses demonstrated that phosphorylation occurs at Ser92, Thr202, and Thr205 of PP2C{\P}. Phosphorylation of these Ser and Thr residues of PP2C{\P} ectopically expressed in 293 cells was enhanced by osmotic stress and was attenuated by a JNK inhibitor but not by p38 or MEK inhibitors. Phosphorylation of PP2C{\P} by TAK1-activated JNK repressed its phosphatase activity in cells, and alanine mutation at Ser92 but not at Thr202 or Thr205 suppressed this inhibition. Taken together, these results suggest that specific phosphorylation of PP2C{\P} at Ser92 by stress-activated JNK attenuates its phosphatase activity in cells.}, address = {Department of Biochemistry and Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan, and Division of Oral Surgery, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan}, author = {Awano, Kenjiro and Amano, Kazutaka and Nagaura, Yuko and Kanno, Shin-Ichiro and Echigo, Seishi and Tamura, Shinri and Kobayashi, Takayasu}, citeulike-article-id = {2894309}, citeulike-linkout-0 = {http://dx.doi.org/10.1021/bi800067p}, citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/bi800067p}, day = {14}, doi = {10.1021/bi800067p}, journal = {Biochemistry}, keywords = {activity, c-jun, phosphatase, phosphorylation}, month = {June}, posted-at = {2008-06-14 07:29:38}, priority = {2}, title = {Phosphorylation of Protein Phosphatase 2C\&\#x3b6; by c-Jun NH2-Terminal Kinase at Ser92 Attenuates Its Phosphatase Activity}, url = {http://dx.doi.org/10.1021/bi800067p}, year = {2008} }

TY - JOUR ID - citeulike:2894309 L3 - citeulike-article-id:2894309 N2 - Abstract: The protein phosphatase 2C (PP2C) family represents one of the four major protein Ser/Thr phosphatase activities in mammalian cells and contains at least 13 distinct gene products. Although PP2C family members regulate a variety of cellular functions, mechanisms of regulation of their activities are largely unknown. Here, we show that PP2C¶, a PP2C family member that is enriched in testicular germ cells, is phosphorylated by c-Jun NH2-terminal kinase (JNK) but not by p38 in vitro. Mass spectrometry and mutational analyses demonstrated that phosphorylation occurs at Ser92, Thr202, and Thr205 of PP2C¶. Phosphorylation of these Ser and Thr residues of PP2C¶ ectopically expressed in 293 cells was enhanced by osmotic stress and was attenuated by a JNK inhibitor but not by p38 or MEK inhibitors. Phosphorylation of PP2C¶ by TAK1-activated JNK repressed its phosphatase activity in cells, and alanine mutation at Ser92 but not at Thr202 or Thr205 suppressed this inhibition. Taken together, these results suggest that specific phosphorylation of PP2C¶ at Ser92 by stress-activated JNK attenuates its phosphatase activity in cells. JF - Biochemistry AD - Department of Biochemistry and Department of Molecular Genetics, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan, and Division of Oral Surgery, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan TI - Phosphorylation of Protein Phosphatase 2Cζ by c-Jun NH2-Terminal Kinase at Ser92 Attenuates Its Phosphatase Activity KW - activity KW - c-jun KW - phosphatase KW - phosphorylation AU - Awano, Kenjiro AU - Amano, Kazutaka AU - Nagaura, Yuko AU - Kanno, Shin-Ichiro AU - Echigo, Seishi AU - Tamura, Shinri AU - Kobayashi, Takayasu PY - 2008/06/14/ UR - http://dx.doi.org/10.1021/bi800067p ER -