Differential regulation of P-selectin expression by protein kinase A and protein kinase G in thrombin-stimulated human platelets
Copyright policy )Differential regulation of P-selectin expression by protein kinase A and protein kinase G in thrombin-stimulated human platelets
SummaryP-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.
- Montreal Heart Institute Canada
Blood Platelets, Indoles, Neutrophils, Colforsin, Carbazoles, Isoquinolines, Platelet Activation, Cyclic AMP-Dependent Protein Kinases, Enzyme Activation, P-Selectin, Alkaloids, Gene Expression Regulation, Cell Adhesion, Cyclic AMP, Cyclic GMP-Dependent Protein Kinases, Humans, Enzyme Inhibitors, Phosphorylation, Cyclic GMP, Adenylyl Cyclases
Blood Platelets, Indoles, Neutrophils, Colforsin, Carbazoles, Isoquinolines, Platelet Activation, Cyclic AMP-Dependent Protein Kinases, Enzyme Activation, P-Selectin, Alkaloids, Gene Expression Regulation, Cell Adhesion, Cyclic AMP, Cyclic GMP-Dependent Protein Kinases, Humans, Enzyme Inhibitors, Phosphorylation, Cyclic GMP, Adenylyl Cyclases
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