Goldschmidt-Clermont P J, Machesky L M, Baldassare J J, Pollard T D
Department of Cell Biology and Anatomy, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Science. 1990 Mar 30;247(4950):1575-8. doi: 10.1126/science.2157283.
Profilin is generally thought to regulate actin polymerization, but the observation that acidic phospholipids dissociate the complex of profilin and actin raised the possibility that profilin might also regulate lipid metabolism. Profilin isolated from platelets binds with high affinity to small clusters of phosphatidylinositol 4,5-bisphosphate (PIP2) molecules in micelles and also in bilayers with other phospholipids. The molar ratio of the complex of profilin with PIP2 is 1:7 in micelles of pure PIP2 and 1:5 in bilayers composed largely of other phospholipids. Profilin competes efficiently with platelet cytosolic phosphoinositide-specific phospholipase C for interaction with the PIP2 substrate and thereby inhibits PIP2 hydrolysis by this enzyme. The cellular concentrations and binding characteristics of these molecules are consistent with profilin being a negative regulator of the phosphoinositide signaling pathway in addition to its established function as an inhibitor of actin polymerization.
通常认为，丝切蛋白可调节肌动蛋白聚合，但酸性磷脂可使丝切蛋白与肌动蛋白的复合物解离，这一现象提示丝切蛋白也可能调节脂质代谢。从血小板中分离出的丝切蛋白，能以高亲和力与微团以及含其他磷脂的双分子层中的小簇磷脂酰肌醇4,5-二磷酸（PIP2）分子结合。在纯PIP2微团中，丝切蛋白与PIP2复合物的摩尔比为1:7，而在主要由其他磷脂构成的双分子层中，该比例为1:5。丝切蛋白能与血小板胞质磷酸肌醇特异性磷脂酶C有效竞争，以与PIP2底物相互作用，从而抑制该酶对PIP2的水解。这些分子的细胞浓度和结合特性表明，丝切蛋白除了作为肌动蛋白聚合的抑制剂这一既定功能外，还是磷酸肌醇信号通路的负调节因子。
