Phospholipase C isozymes as effectors of Ras superfamily GTPases.
The physiological effects of many extracellular stimuli are initiated through receptor-promoted activation of phospholipase C and inositol lipid signaling pathways. The historical view that phospholipase C-promoted signaling primarily occurs through activation of heterotrimeric G proteins or tyrosine kinases has expanded in recent years with the realization that at least three different mammalian phospholipase C isozymes are directly activated by members of the Ras superfamily of GTPases. Thus, Ras, Rap, Rac, and Rho GTPases all specifically regulate certain phospholipase C isozymes, and insight into the physiological significance of these signaling responses is beginning to accrue. High resolution three-dimensional structures of phospholipase C isozymes also are beginning to shed light on their mechanism of activation.
Harden
T Kendall
TK
Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA. tkh@med.unc.edu
Hicks
Stephanie N
SN
Sondek
John
J
D000818:Animals; D004789:Enzyme Activation; D007527:Isoenzymes / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D018631:ras Proteins / Q000145:classification / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D007527:Isoenzymes; D010738:Type C Phospholipases; D020744:rac GTP-Binding Proteins; D018631:ras Proteins; D020741:rho GTP-Binding Proteins