Transcriptional regulation of a receptor protein tyrosine phosphatase gene hPTP-J by PKC-mediated signaling pathways in Jurkat and Molt-4 T lymphoma cells

Biochim Biophys Acta. 1999 Jul 8;1450(3):331-40. doi: 10.1016/s0167-4889(99)00064-6.

Abstract

The recently cloned type II receptor protein tyrosine phosphatase (RPTP) gene hPTP-J is a new member of the MAM (meprin, A5, PTPmicro) domain subfamily. We previously reported that hPTP-J mRNA was detected significantly in Jurkat T lymphoma cells and its expression was completely down-regulated by phorbol myristate acetate (PMA). In this study, we investigated what signaling pathways/molecules are involved in the transcriptional regulation of hPTP-J expression in Jurkat and Molt-4 T cell lines. The hPTP-J transcription was transiently up-regulated 20 min after the addition of PMA (20 ng/ml) to the Jurkat culture, followed by the complete down-regulation in 8 h after PMA addition. The transient up-regulation and the complete down-regulation induced by PMA was blocked by a PKC-specific inhibitor, GF109203X, suggesting that the regulatory effect of PMA on the hPTP-J transcription depends on protein kinase C activation. hPTP-J transcription was down-regulated not only by PMA but also by several signaling modulators including 1-oleoyl-2-acetylglycerol, forskolin, orthovanadate, manumycin and okadaic acid. Therefore, several signaling molecules such as protein tyrosine phosphatases, PP2A/CaMKIV and Ras are required for hPTP-J transcription in Jurkat and Molt-4 cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclic AMP / metabolism
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation / drug effects
  • HL-60 Cells
  • Humans
  • Jurkat Cells
  • Okadaic Acid / pharmacology
  • Protein Kinase C / metabolism*
  • Protein Tyrosine Phosphatases / genetics*
  • Protein Tyrosine Phosphatases / metabolism
  • Receptors, Cell Surface / genetics*
  • Signal Transduction
  • T-Lymphocytes
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transcription, Genetic / drug effects*
  • Tumor Cells, Cultured
  • ras Proteins / metabolism

Substances

  • Enzyme Inhibitors
  • Receptors, Cell Surface
  • Okadaic Acid
  • Cyclic AMP
  • Protein Kinase C
  • Protein Tyrosine Phosphatases
  • ras Proteins
  • Tetradecanoylphorbol Acetate