Abstract
The hematopoietic tyrosine phosphatase (HePTP) is predominantly expressed in thymocytes and T lymphocytes and at lower levels in other hematopoietic cells. Expression of the gene is enhanced by the T cell growth factor interleukin-2, suggesting a role for HePTP in T cell proliferation or differentiation. We report that HePTP blocks T cell antigen receptor (TCR)-induced transcriptional activation of a reporter gene driven by a nuclear factor of activated T cells(NFAT)/AP-1 element taken from the interleukin-2 gene promoter. This effect was specific to HePTP and was abolished by a mutation (C270S) that impaired its phosphatase activity. Co-expression of HePTP also reduced TCR-induced activation of the mitogen-activated protein kinase Erk2 and the TCR-induced appearance of phosphorylated Erk. In contrast, HePTP did not affect the activation of the N-terminal c-Jun kinase, Jnk. Together these findings suggest that HePTP plays an active negative role in TCR signaling by dephosphorylating one or several signaling molecules between the receptor and the mitogen-activated protein kinase pathway.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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DNA-Binding Proteins / metabolism
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Enzyme Activation
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Genes, Reporter
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Humans
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Interleukin-2 / genetics
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Interleukin-2 / metabolism
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Intracellular Signaling Peptides and Proteins
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Jurkat Cells
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Mitogen-Activated Protein Kinase 1
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NFATC Transcription Factors
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Nuclear Proteins*
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Phosphorylation
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases / physiology*
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Protein Tyrosine Phosphatases, Non-Receptor
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Receptors, Antigen, T-Cell / physiology*
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Signal Transduction*
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Transcription Factor AP-1 / metabolism
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Transcription Factors / metabolism
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Transcriptional Activation
Substances
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DNA-Binding Proteins
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Interleukin-2
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Intracellular Signaling Peptides and Proteins
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NFATC Transcription Factors
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Nuclear Proteins
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Receptors, Antigen, T-Cell
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Transcription Factor AP-1
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Transcription Factors
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Calcium-Calmodulin-Dependent Protein Kinases
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Mitogen-Activated Protein Kinase 1
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PTPN6 protein, human
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PTPN7 protein, human
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases
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Protein Tyrosine Phosphatases, Non-Receptor