Nishizuka Y
Philos Trans R Soc Lond B Biol Sci. 1983 Jul 5;302(1108):101-12. doi: 10.1098/rstb.1983.0043.
Turnover of phosphatidylinositol, which is provoked by various neurotransmitters, peptide hormones and many other biologically active substances, appears to serve as a signal for the transmembrane control of protein phosphorylation through activation of a novel protein kinase (C-kinase). The activation of this enzyme absolutely requires Ca2+ and phosphatidylserine. Diacylglycerol derived from the receptor-linked breakdown of phosphatidylinositol dramatically increases the affinity of C-kinase for Ca2+, and thereby renders this enzyme fully active without a net increase in the concentration of Ca2+. Under appropriate conditions synthetic diacylglycerol directly added to intact cell systems activates C-kinase fully without interaction with surface receptors. By using such synthetic diacylglycerol and the Ca2+ ionophore A23187, it is shown that either receptor-linked protein phosphorylation or Ca2+ mobilization alone is merely a prerequisite but not a sufficient requirement, and both are synergistically effective for causing a full physiological cellular response. In some tissues cyclic nucleotides, both cyclic AMP and cyclic GMP, may inhibit the receptor-linked breakdown of phosphatidylinositol, and appear to provide negative control that prevents over-response.
磷脂酰肌醇的周转由多种神经递质、肽类激素和许多其他生物活性物质引发，它似乎通过激活一种新型蛋白激酶（C激酶），作为蛋白质磷酸化跨膜控制的信号。该酶的激活绝对需要Ca2+和磷脂酰丝氨酸。由受体介导的磷脂酰肌醇分解产生的二酰基甘油显著增加了C激酶对Ca2+的亲和力，从而使该酶在Ca2+浓度没有净增加的情况下完全激活。在适当条件下，直接添加到完整细胞系统中的合成二酰基甘油可完全激活C激酶，而无需与表面受体相互作用。通过使用这种合成二酰基甘油和Ca2+离子载体A23187，研究表明，单独的受体介导的蛋白质磷酸化或Ca2+动员仅仅是一个先决条件，但不是充分条件，两者协同作用才能引起完整的生理细胞反应。在某些组织中，环核苷酸，即环磷酸腺苷和环磷酸鸟苷，可能会抑制受体介导的磷脂酰肌醇分解，似乎提供了防止过度反应的负调控。
