Regulation and cellular roles of phosphoinositide 5-kinases.
The membrane phospholipid, phosphatidylinositol 4,5-bisphosphate (PIP(2)), plays a critical role in various, apparently very different cellular processes. As precursor for second messengers generated by phospholipase C isoforms and class I phosphoinositide 3-kinases, PIP(2) is indispensable for cellular signaling by membrane receptors. In addition, PIP(2) directly affects the localization and activity of many cellular proteins via specific interaction with unique phosphoinositide-binding domains and thereby regulates actin cytoskeletal dynamics, vesicle trafficking, ion channel activity, gene expression and cell survival. The activity and subcellular localization of phosphatidylinositol 4-phosphate 5-kinase (PIP5K) isoforms, which catalyze the formation of PIP(2), are actively regulated by membrane receptors, by phosphorylation and by small GTPases of the Rho and ARF families. Spatially and temporally organized regulation of PIP(2) synthesis by PIP5K enables dynamic and versatile PIP(2) signaling and represents an important link in the execution of cellular tasks by Rho and ARF GTPases.
Institut für Pharmakologie, Universitätsklinikum Essen, Hufelandstrasse 55, 45122 Essen, Germany. paschal.oudeweernink@uni-essen.de
Paschal A
PA
Oude Weernink
Martina
M
Schmidt
Karl H
KH
Jakobs
D000818:Animals; D020558:GTP Phosphohydrolases / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism / Q000502:physiology; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000096:biosynthesis*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction
D007527:Isoenzymes; D019269:Phosphatidylinositol 4,5-Diphosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase; D020558:GTP Phosphohydrolases