Abstract
The ZAP-70 tyrosine kinase is a key component of the signaling machinery for the T cell antigen receptor (TCR). Whereas recruitment and activation of ZAP-70 are relatively well understood, the proteins phosphorylated by ZAP-70 are incompletely known. We report here that VHR, a Vaccinia virus VH1-related dual-specific protein phosphatase that inactivates the mitogen-activated kinases Erk2 and Jnk, is phosphorylated at Y138 by ZAP-70. Tyr138 phosphorylation was required for VHR to inhibit the Erk2-Elk-1 pathway and, conversely, the VHR(Y138F) mutant augmented TCR-induced Erk2 kinase and activation of the gene encoding interleukin 2. These results suggest that VHR is a target for ZAP-70 and tempers activation of the Erk2 pathway in a ZAP-70-controlled manner.
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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DNA-Binding Proteins*
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Dual Specificity Phosphatase 3
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Humans
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In Vitro Techniques
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JNK Mitogen-Activated Protein Kinases
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Jurkat Cells
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Lymphocyte Activation
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Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mutagenesis, Site-Directed
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Phosphorylation
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Protein Tyrosine Phosphatases / chemistry
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Protein Tyrosine Phosphatases / genetics
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Protein Tyrosine Phosphatases / metabolism*
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Protein-Tyrosine Kinases / metabolism*
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Proto-Oncogene Proteins / antagonists & inhibitors
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Substrate Specificity
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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Transcription Factors*
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Tyrosine / metabolism
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ZAP-70 Protein-Tyrosine Kinase
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ets-Domain Protein Elk-1
Substances
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DNA-Binding Proteins
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Proto-Oncogene Proteins
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Transcription Factors
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ets-Domain Protein Elk-1
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Tyrosine
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Protein-Tyrosine Kinases
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ZAP-70 Protein-Tyrosine Kinase
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ZAP70 protein, human
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinases
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DUSP3 protein, human
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Dual Specificity Phosphatase 3
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Protein Tyrosine Phosphatases