Dynamic phospholipid signaling by G protein-coupled receptors.
G protein-coupled receptors (GPCRs) control a variety of fundamental cellular processes by regulating phospholipid signaling pathways. Essential for signaling by a large number of receptors is the hydrolysis of the membrane phosphoinositide PIP(2) by phospholipase C (PLC) into the second messengers IP(3) and DAG. Many receptors also stimulate phospholipase D (PLD), leading to the generation of the versatile lipid, phosphatidic acid. Particular PLC and PLD isoforms take differential positions in receptor signaling and are additionally regulated by small GTPases of the Ras, Rho and ARF families. It is now recognized that the PLC substrate, PIP(2), has signaling capacity by itself and can, by direct interaction, affect the activity and subcellular localization of PLD and several other proteins. As expected, the synthesis of PIP(2) by phosphoinositide 5-kinases is tightly regulated as well. In this review, we present an overview of how these signaling pathways are governed by GPCRs, explain the molecular basis for the spatially and temporally organized, highly dynamic quality of phospholipid signaling, and point to the functional connection of the pathways.
Oude Weernink
Paschal A
PA
Institut für Pharmakologie, Universitätsklinikum Essen, Hufelandstrasse 55, 45122 Essen, Germany. paschal.oude-weernink@uni-due.de
Han
Li
L
Jakobs
Karl H
KH
Schmidt
Martina
M
D006801:Humans; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000096:biosynthesis*; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013379:Substrate Specificity
D019269:Phosphatidylinositol 4,5-Diphosphate; D010743:Phospholipids; D020033:Protein Isoforms; D043562:Receptors, G-Protein-Coupled; D010739:Phospholipase D