A novel mitogen-activated protein kinase phosphatase. Structure, expression, and regulation.
Mitogen-activated protein (MAP) kinase lies at the convergence of various extracellular ligand-mediated signaling pathways. It is activated by the dual-specificity kinase, MAP kinase kinase or MEK. MAP kinase inactivation is mediated by dephosphorylation via specific MAP kinase phosphatases (MKPs). One MKP (MKP-1 (also known as 3CH134, Erp, or CL100)) has been reported to be expressed in a wide range of tissues and cells. We report the identification of a second widely expressed MKP, termed MKP-2, isolated from PC12 cells. MKP-2 showed significant homology with MKP-1 (58.8% at the amino acid level) and, like MKP-1, displayed vanadate-sensitive phosphatase activity against MAP kinase in vitro. Overexpression of MKP-2 in vivo inhibited MAP kinase-dependent gene transcription in PC12 cells. MKP-2 differed from MKP-1 in its tissue distribution and in its extent of induction by growth factors and agents that induce cellular stress, suggesting that these MKPs may have distinct physiological functions.
Misra-Press
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Vollum Institute, Oregon Health Sciences University, Portland 97201, USA.
Rim
C S
CS
Yao
H
H
Roberson
M S
MS
Stork
P J
PJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000201:enzymology; D018797:Cell Cycle Proteins; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D054638:Dual Specificity Phosphatase 1; D054637:Dual-Specificity Phosphatases; D015971:Gene Expression Regulation, Enzymologic; D017874:Immediate-Early Proteins / Q000235:genetics; D054639:Mitogen-Activated Protein Kinase Phosphatases; D008969:Molecular Sequence Data; D016716:PC12 Cells; D010749:Phosphoprotein Phosphatases; D011494:Protein Kinases / Q000378:metabolism; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000378:metabolism; D050807:ets-Domain Protein Elk-1
D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C494114:Elk1 protein, rat; D017874:Immediate-Early Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D011494:Protein Kinases; D054639:Mitogen-Activated Protein Kinase Phosphatases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; D054637:Dual-Specificity Phosphatases; C517021:Dusp1 protein, rat; C094132:Dusp4 protein, rat; D017027:Protein Tyrosine Phosphatases