奶油
蛋白激酶C
磷酸化
生物
分子生物学
信号转导
细胞生物学
蛋白激酶A
激酶
响应元素
转录因子
化学
生物化学
基因表达
发起人
基因
作者
E. Gubina,Xu Luo,Evelyn M. Kwon,Kathleen M. Sakamoto,Yufang Shi,R. Allan Mufson
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2001-10-15
卷期号:167 (8): 4303-4310
被引量:29
标识
DOI:10.4049/jimmunol.167.8.4303
摘要
Abstract We have recently shown that IL-3R occupancy activates a phosphatidylcholine-specific phospholipase C, and the sustained diacylglycerol accumulation subsequently activates protein kinase C (PKC). In human IL-3-dependent myeloid cells (TF-1), the novel PKCε isoform regulates bcl-2 expression and cell survival. The report of a PKC activatable cAMP response element (CRE) in the bcl-2 promoter and a role for PKC in bcl-2 expression in B cells led us to the hypothesis that PKC phosphorylation activates transcription factor CREB after IL-3R engagement. We found that IL-3 and GM-CSF induced phosphorylation of CREB on Ser133 in TF-1 cells, and this phosphorylation was blocked by two structurally unrelated classes of PKC inhibitors. An inhibitor of cyclic nucleotide-dependent kinases did not block this phosphorylation. IL-4, which is biologically active in these cells but does not use the β common subunit, did not phosphorylate CREB on Ser133. Inhibition of mitogen-activated protein kinase kinase activity also inhibited IL3-induced CREB phosphorylation. The PKC inhibitors, but not a cyclic nucleotide-dependent kinase inhibitor, blocked IL-3 activation of CRE-dependent transcription from an egr-1 promoter/chloramphenicol acetyltransferase (CAT) reporter construction transiently transfected into TF-1 cells. Finally, TF-1 cells stably overexpressing PKCε, but not the δ isoform of PKC, enhanced CRE-dependent CAT expression from the promoter/reporter construction. Therefore, it is likely that a PKCε kinase cascade resulting in CREB phosphorylation represents a novel signal transduction cascade for regulating cellular gene expression through the β common cytokine receptor.
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