Negative regulation of T cell antigen receptor signal transduction by hematopoietic tyrosine phosphatase (HePTP)

J Biol Chem. 1998 Jun 19;273(25):15340-4. doi: 10.1074/jbc.273.25.15340.

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

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

MeSH terms

  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • DNA-Binding Proteins / metabolism
  • Enzyme Activation
  • Genes, Reporter
  • Humans
  • Interleukin-2 / genetics
  • Interleukin-2 / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Jurkat Cells
  • Mitogen-Activated Protein Kinase 1
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Phosphorylation
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases / physiology*
  • Protein Tyrosine Phosphatases, Non-Receptor
  • Receptors, Antigen, T-Cell / physiology*
  • Signal Transduction*
  • Transcription Factor AP-1 / metabolism
  • Transcription Factors / metabolism
  • Transcriptional Activation

Substances

  • DNA-Binding Proteins
  • Interleukin-2
  • Intracellular Signaling Peptides and Proteins
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Receptors, Antigen, T-Cell
  • Transcription Factor AP-1
  • Transcription Factors
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • PTPN6 protein, human
  • PTPN7 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases
  • Protein Tyrosine Phosphatases, Non-Receptor