Novel mechanisms for feedback regulation of phospholipase C-β activity

Irene Litosch

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

The receptor-regulated phospholipase C-β (PLC-β) signaling pathway is an important component in a network of signaling cascades that regulate cell function. PLC-β signaling has been implicated in the regulation of cardiovascular function and neuronal plasticity. The Gq family of G proteins mediate receptor stimulation of PLC-β activity at the plasma membrane. Mitogens stimulate the activity of a nuclear pool of PLC-β. Stimulation of PLC-β activity results in the rapid hydrolysis of phosphatidylinositol-4,5-bisphosphate, with production of inositol-1,4, 5-trisphosphate and diacylglycerol, intracellular mediators that increase intracellular Ca2+ levels and activate protein kinase C activity, respectively. Diacylglycerol kinase converts diacylglycerol to phosphatidic acid, a newly emerging intracellular mediator of hormone action that targets a number of signaling proteins. Activation of the Gq linked PLC-β signaling pathway can also generate additional signaling lipids, including phosphatidylinositol-3-phosphate and phosphatidylinositol-3,4,5-trisphosphate, which regulate the activity and/or localization of a number of proteins. Novel feedback mechanisms, directed at the level of Gq and PLC-β, have been identified. PLC-β and regulators of G protein signaling (RGS) function as GTPase-activating proteins on Gq to control the amplitude and duration of stimulation. Protein kinases phosphorylate and regulate the activation of specific PLC-β isoforms. Phosphatidic acid regulates PLC-β1 activity and stimulation of PLC-β1 activity by G proteins. These feedback mechanisms coordinate receptor signaling and cell activation. Feedback mechanisms constitute possible targets for pharmacological intervention in the treatment of disease.

Original languageEnglish
Pages (from-to)253-260
Number of pages8
JournalIUBMB Life
Volume54
Issue number5
DOIs
StatePublished - Nov 1 2002
Externally publishedYes

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Keywords

  • G proteins
  • Phosphatidic acid
  • Phospholipase C-β
  • Protein kinases
  • RGS proteins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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