Phospholipase Cγ (PLCγ) expression and activation by a purinergic agonist were investigated in adult rat cardiomyocytes. PLCγ is expressed in isolated cardiomyocytes. Stimulation of cells with extracellular ATP induces a rapid increase in membrane-associated PLCγ immunoreactivity most probably due to redistribution of the lipase from the cytosol to the membrane. The purine triggers a significant phosphorylation on tyrosine residues of a cytosolic pool of PLCγ with a time course that correlates with that of translocation. Extracellular ATP also increases intracellular Ins(1,4,5)P3 content. All these events (translocation and phosphorylation of PLCγ, InsP3 formation) are blocked by genistein, a tyrosine kinase inhibitor. The purinergic effect on both PLCγ translocation and phosphorylation are Ca-sensitive. We thus propose that the purinergic stimulation activates a non-receptor tyrosine kinase that phosphorylates PLCγ in the presence of an increased Ca level and induces PLCγ redistribution to the membrane. There, PLCγ becomes activated leading to the hydrolysis of phosphatidylinositol diphosphate and in turn Ins(1,4,5)P3 formation. This cascade of events may play a significant role in the induction of arrhythmogenesis by purinergic agonists.
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September 1996
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Research Article|
September 01 1996
Purinergic stimulation of rat cardiomyocytes induces tyrosine phosphorylation and membrane association of phospholipase Cγ: a major mechanism for InsP3 generation
Michel PUCEAT;
Michel PUCEAT
*
1INSERM U-390, Laboratoire de Physiopathologie Cardiovasculaire, C.H.U. Arnaud de Villeneuve, 34295 Montpellier Cedex, France
*To whom correspondence should be addressed.
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Guy VASSORT
Guy VASSORT
1INSERM U-390, Laboratoire de Physiopathologie Cardiovasculaire, C.H.U. Arnaud de Villeneuve, 34295 Montpellier Cedex, France
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Publisher: Portland Press Ltd
Received:
March 12 1996
Revision Received:
May 03 1996
Accepted:
May 14 1996
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1996
1996
Biochem J (1996) 318 (2): 723–728.
Article history
Received:
March 12 1996
Revision Received:
May 03 1996
Accepted:
May 14 1996
Citation
Michel PUCEAT, Guy VASSORT; Purinergic stimulation of rat cardiomyocytes induces tyrosine phosphorylation and membrane association of phospholipase Cγ: a major mechanism for InsP3 generation. Biochem J 1 September 1996; 318 (2): 723–728. doi: https://doi.org/10.1042/bj3180723
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