PLC-epsilon: a shared effector protein in Ras-, Rho-, and G alpha beta gamma-mediated signaling.
The conceptual segregation of G protein-stimulated cell signaling responses into those mediated by heterotrimeric G proteins versus those promoted by small GTPases of the Ras superfamily is no longer vogue. PLC-epsilon, an isozyme of the phospholipase C (PLC) family, has been identified recently and dramatically extends our understanding of the crosstalk that occurs between heterotrimeric and small monomeric GTPases. Like the widely studied PLC-beta isozymes, PLC-epsilon is activated by Gbetagamma released upon activation of heterotrimeric G proteins. However, PLC-epsilon markedly differs from the PLC-beta isozymes in its capacity for activation by Galpha(12/13) - but not Galpha(q) -coupled receptors. PLC-epsilon contains two Ras-associating domains located near the C terminus, and H-Ras regulates PLC-epsilon as a downstream effector. Rho also activates PLC-epsilon, but in a mechanism independent of the C-terminal Ras-associating domains. Therefore, Ca(2+) mobilization and activation of protein kinase C are signaling responses associated with activation of both H-Ras and Rho. A guanine nucleotide exchange domain conserved in the N terminus of PLC-epsilon potentially confers a capacity for activators of this isozyme to cast signals into additional signaling pathways mediated by GTPases of the Ras superfamily. Thus, PLC-epsilon is a multifunctional nexus protein that senses and mediates crosstalk between heterotrimeric and small GTPase signaling pathways.
Department of Pharmacology University of North Carolina School of Medicine Chapel Hill, NC 27599, USA.
Michele R
MR
Wing
David M
DM
Bourdon
T Kendall
TK
Harden
D000595:Amino Acid Sequence; D000818:Animals; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D054801:Phosphoinositide Phospholipase C; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D015290:Second Messenger Systems / Q000502:physiology*; D010738:Type C Phospholipases / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D020703:ras GTPase-Activating Proteins / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D007527:Isoenzymes; D020703:ras GTPase-Activating Proteins; D010738:Type C Phospholipases; D054801:Phosphoinositide Phospholipase C; C423320:phospholipase C epsilon; D019204:GTP-Binding Proteins; D020741:rho GTP-Binding Proteins