Abstract

Type I phosphatidylinositol 4-phosphate 5-kinases (PI4P5Ks) phosphorylate phosphatidylinositol 4-phosphate (PI4P) in the 5-position to form phosphatidylinositol 4,5-bisphosphate (PI45P2). The physiological role of type I PI4P 5Ks is self-evidently well established, because their primary function is to synthesize PI45P2. This chapter shows that the substrate specificity of type I and II PIP kinases is dictated largely by their “activation loop”. Studies on substrate specificity have implications also for the localization of type I enzyme. It is demonstrated that changing the substrate specificity from favoring PI4P to PI5P also changes the localization of type Iβ enzyme from plasma membrane to cytosol. This in turn implies that the plasma membrane localization is governed primarily by interaction with the PI4P substrate. The physiological role of type I PI4P 5Ks is self-evidently well established.

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