Transcriptional regulation of a receptor protein tyrosine phosphatase gene hPTP-J by PKC-mediated signaling pathways in Jurkat and Molt-4 T lymphoma cells.
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.
Department of Immunology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
B
B
Wang
K
K
Kishihara
D
D
Zhang
T
T
Sakamoto
K
K
Nomoto
D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D019319:Okadaic Acid / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics*; D015398:Signal Transduction; D013601:T-Lymphocytes; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000378:metabolism
D004791:Enzyme Inhibitors; D011956:Receptors, Cell Surface; D019319:Okadaic Acid; D000242:Cyclic AMP; D011493:Protein Kinase C; D017027:Protein Tyrosine Phosphatases; D018631:ras Proteins; D013755:Tetradecanoylphorbol Acetate