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

Libersan, Danielle;Rousseau, Guy;Merhi, Yahye
(2003) Thrombosis and Haemostasis : international journal for vascular biology and medicine — Vol. 89, n° 2, p. 310-317 (2003)

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  • Libersan, Danielle
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  • Rousseau, GuyUCLouvain
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  • Merhi, Yahye
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Abstract
P-selectin is rapidly translocated from platelet alpha-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 solicited for P-selectin expression when cAMP levels are elevated which suggest a cAMP/PKG-dependent pathway of platelet activation.
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Libersan, D., Rousseau, G., & Merhi, Y. (2003). Differential regulation of P-selectin expression by protein kinase A and protein kinase G in thrombin-stimulated human platelets. Thrombosis and Haemostasis : international journal for vascular biology and medicine, 89(2), 310-317. https://doi.org/10.1267/THRO03020310 (Original work published 2003)