Inhibition of T cell antigen receptor signaling by VHR-related MKPX (VHX), a new dual specificity phosphatase related to VH1 related (VHR).
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.
Alonso
Andres
A
Laboratory of Signal Transduction, La Jolla Cancer Research Center, The Burnham Institute, La Jolla, California 92037, USA.
Merlo
Joseph J
JJ
Na
Songqing
S
Kholod
Natalya
N
Jaroszewski
Lukasz
L
Kharitonenkov
Alexei
A
Williams
Scott
S
Godzik
Adam
A
Posada
James D
JD
Mustelin
Tomas
T
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D018076:DNA, Complementary / Q000378:metabolism; D054640:Dual Specificity Phosphatase 3; D054637:Dual-Specificity Phosphatases; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D019169:Jurkat Cells; D008024:Ligands; D008156:Luciferases / Q000378:metabolism; D008214:Lymphocytes / Q000201:enzymology; D020935:MAP Kinase Signaling System; D051379:Mice; D054639:Mitogen-Activated Protein Kinase Phosphatases; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D013601:T-Lymphocytes / Q000378:metabolism; D013950:Thymus Gland / Q000201:enzymology; D013997:Time Factors; D014018:Tissue Distribution; D014162:Transfection; D014615:Vaccinia / Q000201:enzymology
D018076:DNA, Complementary; D008024:Ligands; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D008156:Luciferases; D005982:Glutathione Transferase; D054639:Mitogen-Activated Protein Kinase Phosphatases; D010744:Phosphoric Monoester Hydrolases; C442824:DUSP22 protein, human; C517025:DUSP3 protein, human; D054640:Dual Specificity Phosphatase 3; D054637:Dual-Specificity Phosphatases; C522152:Dusp22 protein, mouse; C517026:Dusp3 protein, mouse; D017027:Protein Tyrosine Phosphatases