Induction and regulation of human interleukin 2 gene expression: Significance of protein kinase C activation.
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概要
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Phytohemagglutinin (PHA) and a tumor-promoting phorbol ester, 12-O-tetrade-canoylphorbol-13-acetate (TPA) act synergistically to induce interleukin 2 (IL2) mRNA in human lymphocytes in vitro. The induction was inhibited by a potent inhibitor of protein kinase C (C-kinase), 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) at less than 10μM. H-7 inhibited C-kinase activity itself in lymphocytes at the same range of the concentration but did not interfere with the translocation of C-kinase from the cytosol to the membrane fraction of the lymphocytes induced by TPA. H-7 is also known to inhibit cAMP-dependent protein kinase (A-kinase) and cGMP-dependent protein kinase (G-kinase). However, the lymphocytes cultured with dibutyryl cAMP or dibutyryl cGMP could not be activated to produce IL2 mRNA. These results show that activation of C-kinase but not A-kinase and G-kinase is necessary in signal transduction for IL2 gene expression. Prostaglandin E2, which is known to elevate intracellular cAMP level, also inhibited IL2 mRNA induction in the lymphocytes stimulated with PHA and TPA. Addition of α-methylornithine and methylglyoxal his (guanyl hydrazone), which inhibit polyamine synthesis, did not affect the induction of IL2 mRNA in the lymphocytes stimulated with PHA and TPA, indicating that polyamine synthesis is not necessary for IL2 mRNA induction.
- 社団法人 日本生化学会の論文
著者
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KAWAKAMI Kazuyoshi
Department of Internal Medicine and Infectious Diseases, Graduate School of Medicine, University of
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ONOUE Kaoru
Department of Biochemistry, Institute for Medical Immunology, Kumamoto University School of Medicine
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Ohmura Takafumi
Department Of Pharmacy Kumamoto University School Of Medicine
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HIDAKA Hiroyoshi
Department of Pharmacology, Mie University School of Medicine
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HIDAKA Hiroyoshi
Department of Biochemistry, Institute for Developmental Research, Aichi Prefecture Colony
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YAMAMOTO Yusei
Department of Biochemistry, Institute for Medical Immunology, Kumamoto University Medical School
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