Phosphatidylinositol-5-phosphate 4-kinases synthesize phosphatidylinositol-4,5-bisphosphateP2), a key precursor in phosphoinositide signaling that directly modulates the activity of signaling proteins and cellular processes. There are two subfamilies of PIP kinases, type I and II, that generate PtdIns(4,5)P2 from distinct substrate pools. PIP4 type I kinases use PtdIns5P as a substrate, whereas PIP5 type II kinases use PtdIns4P. In mammalian cells, three isoforms of each PIP4K and PIP5K subfamily, encoded by distinct genes, have been characterized. All PIP kinases are stimulated by phosphatidic acid, extensively regulated by ARF and Rho GTPases, and inhibited by protein kinase A and PI-stimulated autophosphorylation.
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