Pike L J
Washington University School of Medicine, Department of Biochemistry and Molecular Biophysics, St. Louis, Missouri 63110.
Endocr Rev. 1992 Nov;13(4):692-706. doi: 10.1210/edrv-13-4-692.
Phosphoinositides play a central role in the transduction of signals for a variety of hormone and growth factor receptors. Multiple derivatives of phosphatidylinositol are present within the cell including phosphatidylinositol 4,5-bisphosphate, the phosphorylated derivative that is hydrolyzed by phospholipase C to produce the two intracellular second messengers, diacylglycerol and inositol 1,4,5-trisphosphate. The synthesis, degradation, and subsequent resynthesis of the phosphoinositides form a metabolic cycle known as the phosphoinositide cycle. The phosphoinositide cycle begins with the phosphorylation of phosphatidylinositol to form phosphatidylinositol 4-phosphate, a reaction catalyzed by phosphatidylinositol 4-kinase. Phosphatidylinositol kinase activity has been reported to be present in a variety of cellular membranes, and multiple isozymes of phosphatidylinositol 4-kinase are present within the cell, suggesting that the product of this reaction may have more than one biological function. The activity of phosphatidylinositol 4-kinase is regulated by growth factors, further underscoring the importance of this enzyme in cellular regulation. Recent data suggest that in addition to serving as substrates for phospholipase C, the polyphosphoinositides may themselves function as intracellular mediators of hormone action. For example, polyphosphoinositides have marked effects on the activity of certain actin binding proteins that may allow these lipids to participate in the regulation of actin polymerization. This review focuses on the properties of the phosphatidylinositol 4-kinases and the potential role of polyphosphoinositides in the regulation of cellular processes.
磷酸肌醇在多种激素和生长因子受体的信号转导中起核心作用。细胞内存在多种磷脂酰肌醇衍生物，包括磷脂酰肌醇4,5-二磷酸，这种磷酸化衍生物会被磷脂酶C水解，产生两种细胞内第二信使——二酰基甘油和肌醇1,4,5-三磷酸。磷酸肌醇的合成、降解及随后的再合成形成了一个称为磷酸肌醇循环的代谢周期。磷酸肌醇循环始于磷脂酰肌醇磷酸化形成磷脂酰肌醇4-磷酸，该反应由磷脂酰肌醇4-激酶催化。据报道，磷脂酰肌醇激酶活性存在于多种细胞膜中，细胞内存在多种磷脂酰肌醇4-激酶同工酶，这表明该反应的产物可能具有不止一种生物学功能。磷脂酰肌醇4-激酶的活性受生长因子调节，这进一步强调了该酶在细胞调节中的重要性。最近的数据表明，除了作为磷脂酶C的底物外，多磷酸肌醇本身可能作为激素作用的细胞内介质发挥作用。例如，多磷酸肌醇对某些肌动蛋白结合蛋白的活性有显著影响，这可能使这些脂质参与肌动蛋白聚合的调节。这篇综述重点关注磷脂酰肌醇4-激酶的特性以及多磷酸肌醇在细胞过程调节中的潜在作用。
