核二酰基甘油kinase-theta被激活以应对alpha-thrombin。
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Bregoli L,博得塞尔JJ,拉贝DM
核二酰基甘油kinase-theta被激活以应对alpha-thrombin。
生物化学杂志。2001年6月29日;276 (26):23288 - 95。Epub 2001年4月17日。
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11309392 (在PubMed]
- 文摘
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目前,有大量的证据表明,核脂类代谢中起关键作用的信号转导级联。从我们实验室以前的工作表明,静止的刺激成纤维细胞与alpha-thrombin导致生产两个原子核中的脂质第二信使:增加核二酰基甘油质量和激活磷脂酶D,它催化磷脂酰胆碱的水解生成磷脂酸。二酰基甘油激酶(DGK)催化磷脂酸甘油二酯的转换,成为一个有吸引力的候选人一个信号转导组件。有大量证据表明,这个活动确实是监管的信号级联(van Blitterswijk,看过的w·J。,Houssa b(1999)化学。理论物理。脂质98年,95 - 108)。在这个报告中,我们表明,添加alpha-thrombin静止IIC9成纤维细胞增加核DGK活动的结果。原子核从静止IIC9分离细胞的检测表明,DGK-theta和DGK-delta都是礼物。我们利用以前的观测,磷脂酰丝氨酸抑制DGK-delta(由Sakane F。Imai表示S。凯,M。,我和田。, and Kanoh, H. (1996) J. Biol. Chem. 271, 8394-8401), and constitutively active RhoA inhibits DGK-theta (reviewed by Houssa, B., de Widt, J., Kranenburg, O., Moolenaar, W. H., and van Blitterswijk, W. J. (1999) J. Biol. Chem. 274, 6820-6822) to identify the activity induced by alpha-thrombin. Constitutively active RhoA inhibited the nuclear stimulated activity, whereas phosphatidylserine did not have an inhibitory effect. In addition, a monoclonal anti-DGK-theta antibody inhibited the alpha-thrombin-stimulated nuclear activity in vitro. These results demonstrate that DGK-theta is the isoform responsive to alpha-thrombin stimulation. Western blot and immunofluorescence microscopy analyses showed that alpha-thrombin induced the translocation of DGK-theta to the nucleus, implicating that this translocation is at least partly responsible for the increased nuclear activity. Taken together, these data are the first to demonstrate an agonist-induced activity of nuclear DGK-theta activity and a nuclear localization of DGK-delta.