Regulation of phospholipase C-beta activity by phosphatidic acid: isoform dependence, role of protein kinase C, and G protein subunits

Biochemistry. 2003 Feb 18;42(6):1618-23. doi: 10.1021/bi026414h.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Heterotrimeric GTP-Binding Proteins / chemistry*
  • Heterotrimeric GTP-Binding Proteins / metabolism
  • Humans
  • Isoenzymes / chemistry
  • Isoenzymes / metabolism*
  • Lipid Bilayers / chemistry
  • Lipid Bilayers / metabolism
  • Phosphatidic Acids / pharmacology*
  • Phospholipase C beta
  • Phosphorylation
  • Protein Binding
  • Protein Kinase C / chemistry*
  • Protein Kinase C beta
  • Protein Kinase C-alpha
  • Protein Subunits / chemistry*
  • Type C Phospholipases / chemistry
  • Type C Phospholipases / metabolism*


  • Isoenzymes
  • Lipid Bilayers
  • Phosphatidic Acids
  • Protein Subunits
  • PRKCA protein, human
  • Protein Kinase C
  • Protein Kinase C beta
  • Protein Kinase C-alpha
  • Type C Phospholipases
  • Phospholipase C beta
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Heterotrimeric GTP-Binding Proteins