Phosphatidylinositol phosphate kinases (PIPK) are kinases that phosphorylate the phosphoinositides PtdInsP and PtdInsP2 that are derivatives of phosphatidylinositol (PtdIns). It has been found that PtdIns is only phosphorylated on three (3,4,5) of its five hydroxyl groups, possibly because D-2 and D-6 hydroxyl groups cannot be phosphorylated because of steric hindrance.Pettitt TR, Dove SK, Lubben A, Calaminus SDJ, Wakelam MJO. Analysis of intact phosphoinositides in biological samples. American Soc f Biochem and Mol Biol 2006; 47:1588-1596 All 7 combinations of phosphorylated PtdIns have been found in animals, all except PtdIns(3,4,5)P3 have been found in plants.Muller-Roeber B, Pical C. Inositol Phospholipid Metabolism in Arabidopsis. Characterized and Putative Isoforms of Inositol Phospholipid Kinase and Phosphoinositide-Specific Phospholipase C. Plant Physiol 2002 130:22–46
PIPKs are today divided into three groups, type I, II and III that share significant sequence homology but differ in the substrate specificities, subcellular localisations and functions.Anderson RA, Boronenkov IV, Doughman SD, Kunz J, Loijens JC . Phosphatidylinositol phosphate kinases, a multifaceted family of signalling enzymes. J Biol Chem 1999; 274:9907-9910 Type 1 are PIPKs that phosphorylate PtdIns4P to PtdIns(4,5)P2 and are called PtdIns4P 5-kinases because they phosphorylate on the D-5 hydroxyl group. Type II PIPKs phosphorylate PtdIns5P at the D-4 site and are called PtdIns5P 4-kinases. And finally PIPKs of type III are PtdIns3P 5-kinases that phosphorylate PtdIns to PtdIns(3,5)P2, which prototype is Fab1 in yeast (see for descriptive picture). The substrate specificity of type I and II depends on the so-called activation loop. The activation loop is a segment of 22 to 27 amino acid residues, located close to the C-terminal end of the catalytic domain in all PIPKs. When the activation loops of a type I and a type II PIPK were swapped, the chimera with type I backbone showed specificity for type II substrate, and vice versa for the other chimera.Kunz J, Wilson MP, Kisseleva M, Hurley JH, Majerus PW, Anderson RA. The activation loop of phosphatidylinositol phosphate kinases determines signaling specificity. Mol Cell 2000 5:1-11
List of PIPKs
Phosphatidylinositol-4-phosphate 3-kinase Phosphatidylinositol-4,5-bisphosphate 3-kinase Phosphatidylinositol-4-phosphate 5-kinase
References