Negative feedback regulation of g q signaling by protein kinase c is disrupted by diacylglycerol kinase ζ in cos-7 cells

Irene Litosch

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Cellular response to G q-linked agonists is shaped by regulatory inputs which determine signal strength and duration. Stimulation of phospholipase C-β (PLC-β) lipase activity results in an increase in the levels of diacylglycerol (DAG) and activation of protein kinase C (PKC) activity. PKC has been implicated in the feedback regulation of G q signaling through actions on PLC-β and phospholipase D (PLD) lipase activity. As PKC activity is modulated by multiple layers of regulation, the physiological impact of PKC on G q signaling is unclear. PKC signaling can be terminated by diacylglycerol kinases (DGKs) which are regulated in a cell-specific manner. The present studies investigated the contribution of the ubiquitously expressed DGKζ isoform in the regulation of PKC signaling and G q response in transfected COS-7 cells. Genetic depletion of DGKζ protein with antisense oligonucleotides dramatically reduced DAG metabolism. The sustained increase in PKC signaling was associated with a pronounced inhibition of carbachol-stimulated lipase activity in cells co-transfected with m1 muscarinic receptor, Gα q and either with or without PLC-β 1. The data also reveal that sustained activation of PKC alone does not increase cellular PLD1 activity. Therefore, G 12-activated RhoA is physiologically important for adequate stimulation of PLD1 activity. These data show that the impact of PKC on G q signal transduction is determined by the background of cell-specific processes.

Original languageEnglish
Pages (from-to)956-960
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume417
Issue number3
DOIs
StatePublished - Jan 20 2012
Externally publishedYes

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Keywords

  • Diacylglycerol kinase
  • G
  • GPCR
  • Phosphatidic acid
  • Phospholipase C-β
  • Protein kinase C

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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