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 language | English (US) |
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Pages (from-to) | 956-960 |
Number of pages | 5 |
Journal | Biochemical and biophysical research communications |
Volume | 417 |
Issue number | 3 |
DOIs | |
State | Published - Jan 20 2012 |
Keywords
- Diacylglycerol kinase
- G
- GPCR
- Phosphatidic acid
- Phospholipase C-β
- Protein kinase C
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Cell Biology
- Molecular Biology