Tada Y, Yoshizawa S, Nagasawa K, Furugo I, Tsuru T, Mayumi T, Tsukamoto H, Niho Y
First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Immunopharmacology. 1992 Jul-Aug;24(1):17-24. doi: 10.1016/0162-3109(92)90065-k.
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.
冈田酸是一种强效的肿瘤促进剂，也是丝氨酸/苏氨酸特异性蛋白磷酸酶的抑制剂。我们研究了冈田酸对人T细胞活化及内部底物磷酸化的影响。高达4 nM的冈田酸增强了佛波酯（PMA）诱导的增殖以及CD25（白细胞介素-2受体，p55）的表达，尽管其自身并无激活作用。如在成纤维细胞和角质形成细胞中所报道的那样，冈田酸在T细胞以及非T细胞中诱导了一种60 kDa蛋白的过度磷酸化。用4 nM冈田酸预孵育增强了PMA诱导的80 kDa蛋白的磷酸化，该蛋白是T细胞中蛋白激酶C的一种内部底物。这些结果表明，冈田酸抑制了蛋白激酶C特异性底物的去磷酸化，结果增强了由蛋白激酶C途径介导的T细胞活化。
