Cockcroft S
Department of Physiology, University College London, UK.
Chem Phys Lipids. 1999 Apr;98(1-2):23-33. doi: 10.1016/s0009-3084(99)00015-8.
Phosphatidylinositol transfer proteins (PITP) are abundant cytosolic proteins found in all mammalian cells. Two cytosolic isoforms of 35 and 36 kDa (PITP alpha and PITP beta) have been identified which share 77% identity. These proteins are characterized by having a single phospholipid binding site which exhibits dual headgroup specificity. The preferred lipid that can occupy the site can be either phosphatidylinositol (PI) or phosphatidylcholine (PC). In addition, PITP beta can also bind sphingomyelin. A second characteristic of these proteins is the ability to transfer PI and PC (or SM) from one membrane compartment to another in vitro. The function of PITP in mammalian cells has been examined mainly using reconstitution studies utilizing semi-intact cells or cell-free systems. From such analyses, a requirement for PITP has been identified in phospholipase C-mediated phosphatidylinositol bisphosphate (PI(4,5)P2) hydrolysis, in phosphoinositide 3-kinase catalyzed PIP3 generation, in regulated exocytosis, in the biogenesis of secretory granules and vesicles and in intra-golgi transport. Studies aimed at elucidating the mechanism of action of PITP in each of these seemingly disparate processes have yielded a singular theme: the activity of PITP stems from its ability to transfer PI from its site of synthesis to sites of cellular activity. This function was predicted from its in vitro characteristics. The second feature of PITP that was not predicted is the ability to stimulate the local synthesis of several phosphorylated forms of PI including PI(4)P, PI(4,5)P2, PI(3)P, PI(3,4,5)P3 by presenting PI to the lipid kinases involved in phosphoinositide synthesis. We conclude that PITP contributes in multiple aspects of cell biology ranging from signal transduction to membrane trafficking events where a central role for phosphoinositides is recognized either as a substrate or as an intact lipid signalling molecule.
磷脂酰肌醇转移蛋白（PITP）是在所有哺乳动物细胞中都能找到的丰富的胞质蛋白。已鉴定出两种胞质异构体，分子量分别为35 kDa和36 kDa（PITPα和PITPβ），它们的同源性为77%。这些蛋白质的特征是具有一个单一的磷脂结合位点，该位点表现出双亲头部特异性。能够占据该位点的首选脂质可以是磷脂酰肌醇（PI）或磷脂酰胆碱（PC）。此外，PITPβ还可以结合鞘磷脂。这些蛋白质的第二个特征是能够在体外将PI和PC（或SM）从一个膜区室转移到另一个膜区室。PITP在哺乳动物细胞中的功能主要通过利用半完整细胞或无细胞系统的重组研究来进行研究。通过此类分析，已确定在磷脂酶C介导的磷脂酰肌醇二磷酸（PI(4,5)P2）水解、磷酸肌醇3激酶催化的PIP3生成、调节性胞吐作用、分泌颗粒和小泡的生物发生以及高尔基体内运输中都需要PITP。旨在阐明PITP在这些看似不同的过程中每一个过程的作用机制的研究得出了一个单一的主题：PITP的活性源于其将PI从合成位点转移到细胞活性位点的能力。该功能是根据其体外特性预测的。PITP的第二个未被预测到的特征是能够通过将PI呈现给参与磷酸肌醇合成的脂质激酶来刺激几种磷酸化形式的PI的局部合成，包括PI(4)P、PI(4,5)P2、PI(3)P、PI(3,4,5)P3。我们得出结论，PITP在细胞生物学的多个方面都有贡献，从信号转导到膜运输事件，其中磷酸肌醇作为底物或完整脂质信号分子都发挥着核心作用。
