Differential regulation of P-selectin expression by protein kinase A and protein kinase G in thrombin-stimulated human platelets

Danielle Libersan; Guy Rousseau; Yahye Merhi

doi:10.1055/s-0037-1613448

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2003; 89(02): 310-317
DOI: 10.1055/s-0037-1613448

Platelets and Blood Cells

Schattauer GmbH

Differential regulation of P-selectin expression by protein kinase A and protein kinase G in thrombin-stimulated human platelets

Authors

Danielle Libersan

¹Montreal Heart Institute, Research Center, Montreal, Quebec, Canada
Guy Rousseau

²Hôpital du Sacré-Cœur, Research Center, Montreal, Quebec, Canada
Yahye Merhi

¹Montreal Heart Institute, Research Center, Montreal, Quebec, Canada

Abstract

Summary

P-selectin is rapidly translocated from platelet α-granules following activation. Intracellular cyclic AMP (cAMP) is a potent inhibitory pathway that results in global downregulation of platelet activation. While cAMP-dependent protein kinase (PKA) has long been considered as the main mediator of cAMP-dependent effects, no study has yet evaluated its effect on P-selectin expression in human platelets. Pretreatment of thrombin-stimulated platelets with forskolin resulted in a concentration-dependent inhibition of P-selectin expression that correlated with adenylyl cyclase activity. Inhibition of PKA with H-89 reversed cAMP-induced inhibition of P-selectin while cGMP-dependent protein kinase (PKG) inhibition with KT5823 significantly potentiated cAMP-dependent inhibition of P-selectin. Similar results were also observed in a platelet/neutrophil binding assay. In conclusion, cAMP-induced inhibition of P-selectin expression is, in large part, mediated through activation of PKA. PKG appears to be sollicited for P-selectin expression when cAMP levels are elevated which suggest a cAMP/PKG-dependent pathway of platelet activation.

Keywords

Platelets - P-selectin - cAMP - PKA - PKG

Full Text

References

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