Diacylglycerol directly stimulates the insulin receptor tyrosine kinase.
Diacylglycerol directly stimulates the insulin receptor tyrosine kinase.
复制标题
二酰甘油直接刺激胰岛素受体酪氨酸激酶。
DOI：
10.1016/0014-5793(96)00006-3
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发表时间：
1996
期刊：
影响因子：
3.5
通讯作者：
Newton,AC
中科院分区：
文献类型：
--
作者：
Arnold,RS;Newton,AC
洗涤剂的研究：脂肪混合胶束显示，二酰甘油直接刺激胰岛素受体的内在酪氨酸激酶活性。动力学分析表明，二酰甘油通过引起胰岛素受体亲和力的显着增加而激活该激酶。相反，二酰甘油对胰岛素受体的催化活性或其与三磷酸腺苷的亲和力没有影响。对胰岛素受体的刺激不是蛋白激酶C激活的结果。首先，佛波酯是一种有效的蛋白激酶C激活剂，对胰岛素受体的活性没有影响。其次，二酰甘油的激活不是立体特异性的，与1，2-二酰甘油激活蛋白激酶C的特异性形成鲜明对比。由于循环中的胰岛素水平低于胰岛素受体阻滞剂或∗胰岛素的Kd，二酰甘油调节受体与配体的亲和力的能力表明，二酰甘油细胞水平的增加直接使受体对胰岛素敏感。
Studies with detergent: lipid mixed micelles reveal that diacylglycerol directly stimulates the intrinsic tyrosine kinase activity of the insulin receptor. Kinetic analyses indicate that diacylglycerol activates the kinase by causing a marked increase in the affinity of the receptor for insulin. In contrast, diacylglycerol has no effect on the insulin receptor's catalytic activity or its affinity for ATP. Stimulation of the insulin receptor is not a result of protein kinase C activation. First, phorbol myristate acetate, a potent activator of protein kinase C, has no effect on insulin receptor activity. Second, the activation by diacylglycerol is not stereospecific, in marked contrast to the specificity for 1,2‐diacyl‐sn‐glycerol in the activation of protein kinase C. Because circulating levels of insulin are below theKdof the insulin receptor forcor∗ insulin, the ability of diacylglycerol to modulate the affinity of the receptor for ligand suggests that increases in cellular levels of diacylglycerol directly sensitize the receptor to insulin.