PLC-ε: A Shared Effector Protein in Ras-, Rho-, and Gαβγ-Mediated Signaling

PLC-ε : A nexus for heterotrimeric and small G protein signaling pathways. Phospholipase C activity of PLC-ε is stimulated by Gα_12/13, Gβγ, and activated members of Ras and Rho small GTPases to yield downstream second messengers Ins(1,4,5)P₃ and diacylglycerol. In addition, ERK signaling pathways are propagated as a result of the guanine nucleotide exchange activity of the PLC-ε CDC25 domain. A positive feedback loop is schematized in which CDC25-promoted activation of H-Ras and/or Rap1A in turn activates the lipase activity of PLC-ε upon binding the C-terminal RA domains (dashed line). See text for details. (AC, adenylyl cyclase; Shc, SH2 domain–containing adaptor protein; IRS, insulin receptor substrate; Grb2, growth factor receptor–bound protein 2; Sos, son of sevenless GEF; MEK, mitogen-activated protein kinase kinase.)