Abstract
A cDNA encoding a novel, human, dual-specific protein phosphatase was identified in the Incyte data base. The open reading frame predicted a protein of 184 amino acids related to the Vaccinia virus VH1 and human VH1-related (VHR) phosphatases. Expression VHR-related MKPX (VHX) was highest in thymus, but also detectable in monocytes and lymphocytes. A VHX-specific antiserum detected a protein with an apparent molecular mass of 19 kDa in many cells, including T lymphocytes and monocytes. VHX expression was not induced by T cell activation, but decreased somewhat at later time points. In vitro, VHX dephosphorylated the Erk2 mitogen-activated protein kinase with faster kinetics than did VHR, which is thought to be specific for Erk1 and 2. When expressed in Jurkat T cells, VHX had the capacity to suppress T cell antigen receptor-induced activation of Erk2 and of an NFAT/AP-1 luciferase reporter, but not an NF-kappaB reporter. Thus, VHX is a new member of the VH1/VHR group of small dual-specific phosphatases that act in mitogen-activated protein kinase signaling pathways.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Cell Line
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DNA, Complementary / metabolism
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Dual Specificity Phosphatase 3
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Dual-Specificity Phosphatases
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Glutathione Transferase / metabolism
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Humans
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Immunoblotting
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Jurkat Cells
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Ligands
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Luciferases / metabolism
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Lymphocytes / enzymology
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MAP Kinase Signaling System
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Mice
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Mitogen-Activated Protein Kinase Phosphatases
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Phosphoric Monoester Hydrolases / metabolism
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Phosphorylation
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Plasmids / metabolism
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Protein Binding
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Protein Tyrosine Phosphatases / chemistry*
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Protein Tyrosine Phosphatases / metabolism*
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Recombinant Fusion Proteins / metabolism
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Recombinant Proteins / metabolism
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Repressor Proteins*
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Reverse Transcriptase Polymerase Chain Reaction
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Sequence Homology, Amino Acid
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Substrate Specificity
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T-Lymphocytes / metabolism
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Thymus Gland / enzymology
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Time Factors
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Tissue Distribution
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Transfection
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Vaccinia / enzymology
Substances
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DNA, Complementary
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Ligands
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Recombinant Fusion Proteins
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Recombinant Proteins
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Repressor Proteins
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Luciferases
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Glutathione Transferase
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Mitogen-Activated Protein Kinase Phosphatases
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Phosphoric Monoester Hydrolases
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DUSP22 protein, human
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DUSP3 protein, human
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Dual Specificity Phosphatase 3
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Dual-Specificity Phosphatases
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Dusp22 protein, mouse
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Dusp3 protein, mouse
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Protein Tyrosine Phosphatases