Inhibition of T cell antigen receptor signaling by VHR-related MKPX (VHX), a new dual specificity phosphatase related to VH1 related (VHR)

J Biol Chem. 2002 Feb 15;277(7):5524-8. doi: 10.1074/jbc.M107653200. Epub 2001 Dec 3.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • DNA, Complementary / metabolism
  • Dual Specificity Phosphatase 3
  • Dual-Specificity Phosphatases
  • Glutathione Transferase / metabolism
  • Humans
  • Immunoblotting
  • Jurkat Cells
  • Ligands
  • Luciferases / metabolism
  • Lymphocytes / enzymology
  • MAP Kinase Signaling System
  • Mice
  • Mitogen-Activated Protein Kinase Phosphatases
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Phosphoric Monoester Hydrolases / metabolism
  • Phosphorylation
  • Plasmids / metabolism
  • Protein Binding
  • Protein Tyrosine Phosphatases / chemistry*
  • Protein Tyrosine Phosphatases / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Proteins / metabolism
  • Repressor Proteins*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Substrate Specificity
  • T-Lymphocytes / metabolism
  • Thymus Gland / enzymology
  • Time Factors
  • Tissue Distribution
  • Transfection
  • Vaccinia / enzymology

Substances

  • DNA, Complementary
  • Ligands
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • Repressor Proteins
  • Luciferases
  • Glutathione Transferase
  • Mitogen-Activated Protein Kinase Phosphatases
  • Phosphoric Monoester Hydrolases
  • DUSP22 protein, human
  • DUSP3 protein, human
  • Dual Specificity Phosphatase 3
  • Dual-Specificity Phosphatases
  • Dusp22 protein, mouse
  • Dusp3 protein, mouse
  • Protein Tyrosine Phosphatases