Okadaic acid enhances human T cell activation and phosphorylation of an internal substrate induced by phorbol myristate acetate.
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.
Tada
Y
Y
First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Yoshizawa
S
S
Nagasawa
K
K
Furugo
I
I
Tsuru
T
T
Mayumi
T
T
Tsukamoto
H
H
Niho
Y
Y
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*
D004988:Ethers, Cyclic; D010835:Phytohemagglutinins; D011506:Proteins; D015375:Receptors, Interleukin-2; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases; D013755:Tetradecanoylphorbol Acetate