Journal ArticleDOI
Regulation of Phospholipase C-β Activity by Phosphatidic Acid: Isoform Dependence, Role of Protein Kinase C, and G Protein Subunits†
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TLDR
It is demonstrated that PA stimulation of PLC-beta activity is tightly regulated, suggesting the existence of a distinct PA binding region in PL-beta(1), and PA may be an important component of a receptor mediated signaling mechanism that determines P LC- beta(1) activation.Abstract:
Phosphatidic acid (PA) stimulates phospholipase C-beta(1) (PLC-beta(1)) activity and promotes G protein stimulation of PLC-beta(1) activity. The isoform dependence for PA regulation of PLC-beta activity as well as the role of PA in modulating regulation of PLC-beta activity by protein kinase C (PKC) and G protein subunits was determined. As compared to PLC-beta(1), the phospholipase C-beta(3) (PLC-beta(3)) isoform was less sensitive to PA, requiring greater than 15 mol % PA for stimulation. PLC-beta(3) bound weakly to PA. PKC had little effect on PA stimulation of PLC-beta(3) activity. PKC, however, inhibited PA stimulation of PLC-beta(1) activity through a mechanism dependent on the mol % PA. Stimulation by 7.5 mol % PA was completely inhibited by PKC. Increasing the PA and Ca(2+) concentration attenuated PKC inhibition. The binding of PLC-beta(1) to PA containing phospholipid vesicles was also reduced by PKC, in a manner dependent on the mol % PA. PA increased the stimulation of PLC-beta(1) activity by G alpha q but had little effect on the stimulation by beta gamma subunits. These results demonstrate that PA stimulation of PLC-beta activity is tightly regulated, suggesting the existence of a distinct PA binding region in PLC-beta(1). PA may be an important component of a receptor mediated signaling mechanism that determines PLC-beta(1) activation.read more
Citations
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References
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Journal ArticleDOI
The cAMP-specific Phosphodiesterase PDE4D3 Is Regulated by Phosphatidic Acid Binding CONSEQUENCES FOR cAMP SIGNALING PATHWAY AND CHARACTERIZATION OF A PHOSPHATIDIC ACID BINDING SITE
Muriel Grange,Claudio Sette,Margherita Cuomo,Marco Conti,Michel Lagarde,Annie-France Prigent,Georges Némoz +6 more
TL;DR: Investigation of the effect of endogenous PA on PDE activity of transiently transfected MA10 cells overexpressing the PA-sensitive isoform PDE4D3 suggests that endogenous PA can modulate cAMP levels in intact cells, through a direct activation of PDE 4D3.