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Cell Signal. 2000 Oct;12(9-10):645-8.

Lysophosphatidic acid-induced platelet shape change proceeds via Rho/Rho kinase-mediated myosin light-chain and moesin phosphorylation.

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Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Pettenkoferstr. 9, 80336, München, Germany.


Platelet activation plays an important role in arterial thrombotic disorders. Here we show that the serum-borne phospholipid lysophosphatidic acid (LPA) activates the GTPase Rho and its target Rho-kinase to induce myosin light-chain (MLC) and moesin phosphorylation, leading to platelet shape change. MLC phosphorylation, moesin phosphorylation, and shape change were blocked by preincubating platelets with C3 transferase from Clostridium botulinum and Y-27632-specific inhibitors of Rho and Rho kinase, respectively. LPA did not increase the cytosolic Ca(2+) concentration during shape change. Our results suggest that LPA via Rho-Rho kinase induces MLC and moesin phosphorylation leading to shape change in the absence of an increase in the cytosolic Ca(2+) concentration. Rho/Rho kinase inhibition could be a therapeutic strategy to prevent pathologic platelet activation during arterial thrombotic disorders.

[Indexed for MEDLINE]

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