Regulating G protein activity by lipase-independent functions of phospholipase C

Irene Litosch

Research output: Contribution to journalArticle

10 Scopus citations


Abstract The phosphatidylinositol-specific phospholipase C (PLC) family is known to regulate physiological response through an increase in the levels of cytosolic Ca<sup>2 +</sup>. PLC hydrolyzes phosphatidylinositol-4, 5-bisphosphate (PIP<inf>2</inf>) to inositol-1, 4, 5-trisphosphate (IP<inf>3</inf>) and diacylglycerol (DAG). IP<inf>3</inf> releases the stored pool of Ca<sup>2 +</sup>. DAG stimulates protein kinase C (PKC) activity. An intriguing story is that some PLCs are also GTPase activating proteins (GAPs) or guanine nucleotide exchange factors (GEFs) to regulate the activity of their G protein. GEF and GAPs modulate the G protein GTPase cycle. GEFs catalyze the replacement of GDP with GTP to activate the G protein. GAPs accelerate the GTPase cycle to limit signaling upon removal of the activating ligand. It is not known whether GAP/GEF activity is coupled to the lipase activity of PLC, nor is it clear whether or how lipid factors may contribute to this synergistic interaction. While lipase activity is subject to allosteric regulation by mechanisms that include the signaling phospholipid, phosphatidic acid, regulation of the lipase associated GAP/GEF activity remains unexplored. This review explores the possibilities and evidence that support synergistic lipase-G protein regulatory activity in the PLC-β, PLC-δ, PLC-ε and PLC-γ subfamilies that may be mediated, in part, through phosphatidic acid. Understanding the full spectrum of PLC activities, and their regulation, is necessary to drive innovation in medicine by identifying novel targets.

Original languageEnglish (US)
Article number14461
Pages (from-to)116-124
Number of pages9
JournalLife Sciences
StatePublished - Aug 11 2015
Externally publishedYes


  • Ca<sup>2+</sup>
  • G protein-coupled receptor
  • G proteins
  • GTPase activating protein
  • Guanine nucleotide exchange factors
  • Phosphatidic acid
  • Phospholipase C-β

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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