PLCε mediated sustained signaling pathways

Adv Biol Regul. 2015 Jan;57:17-23. doi: 10.1016/j.jbior.2014.09.014. Epub 2014 Oct 5.


Phospholipase C-ε (PLCε) integrates signaling from G-protein coupled receptors (GPCRs) to downstream kinases to regulate a broad range of biological and pathophysiological responses. Relative to other PLCs, PLCε is unique in that it not only serves a catalytic function in phosphoinositide hydrolysis but also functions as an exchange factor small the low molecular weight G-protein Rap1. PLCε is selectively stimulated by agonists for GPCRs that couple to RhoA, which bind directly to the enzyme to regulate its activity. Rap1 also regulates PLCε activity by binding to its RA2 domain and this generates a feedback mechanism allowing sustained signaling. As a result of its regulation by inflammatory ligands for GPCRs and its ability to promote chronic signals, PLCε has been implicated in diseases ranging from cancer to ischemia/reperfusion injury. This review will discuss the regulation of PLCε, molecular mechanisms that contribute to sustained signaling, and the role of the enzyme in various disease contexts.

Keywords: Diacylglycerol (DAG); G-protein coupled receptors (GPCRs); Golgi; Inositol 1,4,5-trisphosphate (IP3); Phosphatidylinositol4,5-bisphosphate (PIP2); Phospholipase C-ε (PLCε); Protein kinase D(PKD); Rap1; Ras; RhoA.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Humans
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Phosphatidylinositols / genetics
  • Phosphatidylinositols / metabolism
  • Phosphoinositide Phospholipase C / genetics
  • Phosphoinositide Phospholipase C / metabolism*
  • Protein Structure, Tertiary
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Reperfusion Injury / genetics
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / pathology
  • Shelterin Complex
  • Signal Transduction*
  • Telomere-Binding Proteins / genetics
  • Telomere-Binding Proteins / metabolism
  • rhoA GTP-Binding Protein / genetics
  • rhoA GTP-Binding Protein / metabolism


  • Neoplasm Proteins
  • Phosphatidylinositols
  • Receptors, G-Protein-Coupled
  • Shelterin Complex
  • TERF2IP protein, human
  • Telomere-Binding Proteins
  • RHOA protein, human
  • Phosphoinositide Phospholipase C
  • phospholipase C epsilon
  • rhoA GTP-Binding Protein