Phosphatidylinositol signalling reactions.
Phosphatidylinositols are important in intracellular signaling. In response to extracellular signals, these molecules undergo rapid turnover and generate second messengers including diacylglycerol, inositol 1,4,5-trisphosphate, phosphatidylinositol 3,4-bisphosphate (PtdIns 3,4P2) and phosphatidylinositol 3,4,5-trisphosphate (PtdIns 3,4,5-P3). The importance of phosphoinositide metabolism is underscored by its link to a human genetic disorder oculocerebrorenal syndrome of Lowe in that the gene product (OCRL) deficient in this syndrome is an inositol polyphosphate 5-phosphatase. A new pathway for formation of PtdIns 3,4-P2 and PtdIns 3,4,5-P3 has been found recently. PtdIns 4,5-P2-synthesizing enzymes phosphatidylinositol 4-phosphate 5-kinases (PIP5K) also have kinase activity towards PtdIns 3-P and PtdIns 3,4-P2 forming PtdIns 3,4-P2 and PtdIns 3,4,5-P3 respectively. Surprisingly, they can synthesize PtdIns 3,4,5-P3 directly from PtdIns 3-P in a concerted reaction. PIP5K isozymes may play pivotal roles in intracellular signaling.
Zhang
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Department of Internal Medicine, Washington University, School of Medicine, St. Louis, Missouri 63110, USA.
Majerus
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D000818:Animals; D006801:Humans; D000072181:Inositol Polyphosphate 5-Phosphatases; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D009800:Oculocerebrorenal Syndrome / Q000201:enzymology / Q000235:genetics; D010716:Phosphatidylinositols / Q000502:physiology*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D007527:Isoenzymes; D010716:Phosphatidylinositols; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases