Calcium, phospholipid turnover and transmembrane signalling.

Calcium, phospholipid turnover and transmembrane signalling.
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钙、磷脂周转和跨膜信号传导。

DOI:
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发表时间:
1983
期刊:
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
影响因子:
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通讯作者:
Y. Nishizuka
Y. Nishizuka
中科院分区:
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文献类型:
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作者:
Y. Nishizuka

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磷脂酰肌醇的周转由多种神经递质、多肽激素和许多其他生物活性物质引起,它似乎是一种信号,通过激活一种新的蛋白激酶(C-激酶)来跨膜控制蛋白质的磷酸化。这种酶的激活绝对需要钙离子和磷脂酰丝氨酸。由磷脂酰肌醇受体连接的裂解而来的二酰甘油极大地增加了C-激酶对钙离子的亲和力,从而使该酶在不增加钙离子浓度的情况下完全激活。在适当的条件下,合成的二酰甘油直接加入到完整的细胞系统中,可以完全激活C-激酶,而不与表面受体相互作用。通过使用这种合成的二酰甘油和钙离子载体A23187,结果表明,受体连接蛋白的磷酸化或单独的钙动员只是一个先决条件,而不是充分的要求,两者对于引起全面的生理细胞反应是协同有效的。在一些组织中,环核苷酸,包括环AMP和环GMP,可能会抑制磷脂酰肌醇与受体相连的分解,并似乎提供了防止过度反应的负面控制。
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.