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Platelet activation—a role for a 40K anti-phospholipase A2 protein indistinguishable from lipocortin

Nature volume 321, pages 177180 (08 May 1986) | Download Citation

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Abstract

Stimulus–response (S–R) coupling in platelets requires an intermediary other than an elevation in cytosolic free calcium ([Ca2+]i)1,2. While an increase in [Ca2+]i is essential in S–R coupling, effecting phosphorylation of myosin of relative molecular mass (Mr) 20,000 (20 K)3, platelet activation is also associated with phosphorylation of a 40K protein4, which can occur in the absence of changes in [Ca2+]i (ref. 5). The 40K protein is the substrate for protein kinase C (PKC)6,7. Mounting evidence suggests that activation of PKC by diacyglycerol is the other signal involved in S–R coupling6,8–10. Although phosphorylation of the 40K protein is associated with certain platelet functional responses4,6,8,11,12, no precise role has been accredited to it. Recently, we and others have described several proteins (collectively known as lipocortin) which inhibit phospholipase A2 (PLA2)13–19. One of the most conspicuous proteins of this group is a 40K peptide whose inhibitory activity can be suppressed by prior phosphorylation18,20. We hypothesized that the 40K protein described in platelets may possess anti-PLA2 activity and that phosphorylation by PKC, suppressing its inhibitory activity, may represent the mechanism underlying mobilization of arachidonic acid, the precursor of prostaglandins. The results of the present study strongly support this hypothesis.

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  1. Unité associée Institut Pasteur/Inserm No. 285, Institut Pasteur, 28 rue du Dr Roux, 75015 Paris, France

    • Lhousseine Touqui
    • , Bernard Rothhut
    • , Angus M. Shaw
    • , Armel Fradin
    • , B. Boris Vargaftig
    •  & Françoise Russo-Marie

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https://doi.org/10.1038/321177a0

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