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.
Wing
Michele R
MR
Department of Pharmacology University of North Carolina School of Medicine Chapel Hill, NC 27599, USA.
Bourdon
David M
DM
Harden
T Kendall
TK
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