SPECIFICITY AND MECHANISM OF PROTEIN-KINASE-C ACTIVATION BY SN-1,2-DIACYLGLYCEROLS
SPECIFICITY AND MECHANISM OF PROTEIN-KINASE-C ACTIVATION BY SN-1,2-DIACYLGLYCEROLS
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DOI：
10.1073/pnas.83.5.1184
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发表时间：
1986-03-01
影响因子：
11.1
通讯作者：
BELL, RM
中科院分区：
文献类型：
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作者：
GANONG, BR;LOOMIS, CR;BELL, RM
通过使用 Triton X-100 混合胶束测定法研究 sn-1,2-二酰基甘油和类似物激活蛋白激酶 C 的特异性 [Hannum, Y. A., Loomis, C. R. 和 Bell, R. M. (1985) J. Biol.化学。 260、10039-10043]。合成了含有长度为 8 个碳的酰基或烷基链的类似物，因为 sn-1,2-二辛酰甘油是蛋白激酶 C 的有效细胞渗透激活剂。这些类似物作为大鼠脑蛋白激酶 C 的激活剂和拮抗剂进行了测试，以确定对活性重要的确切结构特征。类似物证实二酰基甘油对蛋白激酶C的激活具有高度特异性。几种类似物证实，氧酯的两个羰基部分都是最大活性所必需的，并且还需要3-羟基部分。没有一个类似物是拮抗剂。这些数据与之前的研究相结合，可以制定蛋白激酶 C 激活模型。 sn-1,2-二酰基甘油与表面结合蛋白激酶 C-磷脂酰丝氨酸-Ca2+ 复合物的三点连接预计会引起激活。推测二酰甘油与 Ca2+ 的直接连接是蛋白激酶 C 激活机制中的一个重要步骤。
The specificity of protein kinase C activation by sn-1,2-diacylglycerols and analogues was investigated by using a Triton X-100 mixed micellar assay [Hannum, Y. A., Loomis, C. R. and Bell, R. M. (1985) J. Biol. Chem. 260, 10039-10043]. Analogues containing acyl or alkyl chains eight carbons in length were synthesized because sn-1,2-dioctanoylglycerol is an effective cell-permeant activator of protein kinase C. These analogues were tested as activators and antagonists of rat brain protein kinase C to determine the exact structural features important for activity. The analogues established that activation of protein kinase C by diacylglycerols is highly specific. Several analogues established that both carbonyl moieties of the oxygen esters are required for maximal activity and that the 3-hydroxyl moiety is also required. None of the analogues were antagonists. These data, combined with previous investigations, permitted formulation of a model of protein kinase C activation. A three-point attachment of sn-1,2-diacylglycerol to the surface-bound protein kinase C-phosphatidylserine-Ca2+ complex is envisioned to cause activation. Direct ligation of diacylglycerol to Ca2+ is proposed to be an essential step in the mechanism of activation of protein kinase C.