Regulation of phospholipase C-β activity by phosphatidic acid

Isoform dependence, role of protein kinase C, and G protein subunits

Irene Litosch

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Phosphatidic acid (PA) stimulates phospholipase C-β1 (PLC-β1) activity and promotes G protein stimulation of PLC-β1 activity. The isoform dependence for PA regulation of PLC-β activity as well as the role of PA in modulating regulation of PLC-β activity by protein kinase C (PKC) and G protein subunits was determined. As compared to PLC-β1, the phospholipase C-β3 (PLC-β3) isoform was less sensitive to PA, requiring greater than 15 mol % PA for stimulation. PLC-β3 bound weakly to PA. PKC had little effect on PA stimulation of PLC-β3 activity. PKC, however, inhibited PA stimulation of PLC-β1 activity through a mechanism dependent on the mol % PA. Stimulation by 7.5 mol % PA was completely inhibited by PKC. Increasing the PA and Ca2+ concentration attenuated PKC inhibition. The binding of PLC-β1 to PA containing phospholipid vesicles was also reduced by PKC, in a manner dependent on the mol % PA. PA increased the stimulation of PLC-β1 activity by Gαq but had little effect on the stimulation by βy subunits. These results demonstrate that PA stimulation of PLC-β activity is tightly regulated, suggesting the existence of a distinct PA binding region in PLC-β1. PA may be an important component of a receptor mediated signaling mechanism that determines PLC-β1 activation.

Original languageEnglish
Pages (from-to)1618-1623
Number of pages6
JournalBiochemistry
Volume42
Issue number6
DOIs
StatePublished - Feb 18 2003
Externally publishedYes

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Cyclic GMP-Dependent Protein Kinases
Phosphatidic Acids
Protein Subunits
Type C Phospholipases
GTP-Binding Proteins
Protein Kinase C
Protein Isoforms
Programmable logic controllers

ASJC Scopus subject areas

  • Biochemistry

Cite this

Regulation of phospholipase C-β activity by phosphatidic acid : Isoform dependence, role of protein kinase C, and G protein subunits. / Litosch, Irene.

In: Biochemistry, Vol. 42, No. 6, 18.02.2003, p. 1618-1623.

Research output: Contribution to journalArticle

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abstract = "Phosphatidic acid (PA) stimulates phospholipase C-β1 (PLC-β1) activity and promotes G protein stimulation of PLC-β1 activity. The isoform dependence for PA regulation of PLC-β activity as well as the role of PA in modulating regulation of PLC-β activity by protein kinase C (PKC) and G protein subunits was determined. As compared to PLC-β1, the phospholipase C-β3 (PLC-β3) isoform was less sensitive to PA, requiring greater than 15 mol {\%} PA for stimulation. PLC-β3 bound weakly to PA. PKC had little effect on PA stimulation of PLC-β3 activity. PKC, however, inhibited PA stimulation of PLC-β1 activity through a mechanism dependent on the mol {\%} PA. Stimulation by 7.5 mol {\%} PA was completely inhibited by PKC. Increasing the PA and Ca2+ concentration attenuated PKC inhibition. The binding of PLC-β1 to PA containing phospholipid vesicles was also reduced by PKC, in a manner dependent on the mol {\%} PA. PA increased the stimulation of PLC-β1 activity by Gαq but had little effect on the stimulation by βy subunits. These results demonstrate that PA stimulation of PLC-β activity is tightly regulated, suggesting the existence of a distinct PA binding region in PLC-β1. PA may be an important component of a receptor mediated signaling mechanism that determines PLC-β1 activation.",
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