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

The recently cloned type II receptor protein tyrosine phosphatase (RPTP) ge ne hPTP-J is a new member of the MAM (meprin, A5, PTP mu) domain subfamily. We previously reported that hPTP-J mRNA was detected significantly in Jurk at T lymphoma cells and its expression was completely down-regulated by pho rbol 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 wa s transiently up-regulated 20 min after the addition of PMA (20 ng/ml) to t he Jurkat culture, followed by the complete down-regulation in 8 h after PM A addition. The transient up-regulation and the complete down-regulation in duced by PMA was blocked by a PKC-specific inhibitor, GF109203X, suggesting that the regulatory effect of PMA on the hPTP-J transcription depends on p rotein kinase C activation. hPTP-J transcription was down-regulated not onl y by PMA but also by several signaling modulators including 1-oleoyl-2-acet ylglycerol, forskolin, orthovanadate, manumycin and okadaic acid. Therefore , several signaling molecules such as protein tyrosine phosphatases, PP2A/C aMK1V and Ras are required for hPTP-J transcription in Jurkat and Molt-1 ce lls. (C) 1999 Elsevier Science B.V. All rights reserved.