title: Okadaic acid enhances human T cell activation and phosphorylation of an internal substrate induced by phorbol myristate acetate.
abstract: Okadaic acid is a potent tumor promoter and an inhibitor of serine/threonine-specific protein phosphatases. We studied the effect of okadaic acid in human T cell activation and phosphorylation of internal substrates. Okadaic acid at up to 4 nM enhanced phorbol myristate acetate (PMA)-induced proliferation and CD25 (IL-2 receptor, p55) expression, although it showed no activation by itself. Okadaic acid induced hyperphosphorylation of a 60 kDa protein in T cells as well as non-T cells, as reported in fibroblasts and keratinocytes. Preincubation with 4 nM okadaic acid enhanced PMA induced phosphorylation of the 80 kDa protein, an internal substrate of protein kinase C in T cells. These results suggest that okadaic acid inhibited dephosphorylation of protein kinase C specific substrates, and as a result, enhanced T cell activation mediated by protein kinase C pathway.
authors.affiliation: First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tada
authors.forename: S
authors.initials: S
authors.lastname: Yoshizawa
authors.forename: K
authors.initials: K
authors.lastname: Nagasawa
authors.forename: I
authors.initials: I
authors.lastname: Furugo
authors.forename: T
authors.initials: T
authors.lastname: Tsuru
authors.forename: T
authors.initials: T
authors.lastname: Mayumi
authors.forename: H
authors.initials: H
authors.lastname: Tsukamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Niho
mesh_terms: D004988:Ethers, Cyclic / Q000494:pharmacology*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D010835:Phytohemagglutinins; D011506:Proteins / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D004988:Ethers, Cyclic; D010835:Phytohemagglutinins; D011506:Proteins; D015375:Receptors, Interleukin-2; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases; D013755:Tetradecanoylphorbol Acetate