Platelet P-selectin expression: requirement for protein kinase C, but not protein tyrosine kinase or phosphoinositide 3-kinase.
P-selectin is translocated from the alpha-granules to the surface of activated platelets where it participates in thrombosis and inflammation. We investigated the signaling pathways involved in thrombin-induced human platelet P-selectin expression. Assessed by flow cytometry, inhibition of protein kinase C (PKC) with chelerythrine reduced P-selectin expression by 66%, platelet/neutrophil binding, GPIIb/IIIa activation and aggregation (p<0.05). Gö 6976, an inhibitor of the conventional PKCs (alpha and beta), did not alter P-selectin expression. However, rottlerin inhibited by 50% its expression (p<0.05), but only at doses that interfere with the novel (epsilon eta) and atypical (zeta) PKCs. Inhibition of protein tyrosine kinase (PTK) and phosphoinosi-tide 3-kinase (PI3-K) did not significantly affect P-selectin expression. In conclusion, thrombin-induced P-selectin expression is PKC-sensitive, but PTK and PI3-K-insensitive. The novel epsilon and eta and atypical zeta, but not the conventional alpha and beta and the novel delta PKCs, may be involved in this process.
Libersan
Danielle
D
Montreal Heart Institute and the University of Montreal, Quebec, Canada.
Merhi
Yahye
Y
D001792:Blood Platelets / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007527:Isoenzymes / Q000502:physiology; D019007:P-Selectin / Q000032:analysis / Q000096:biosynthesis*; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C / Q000502:physiology*; D011505:Protein-Tyrosine Kinases; D022142:Secretory Vesicles / Q000378:metabolism; D015398:Signal Transduction; D013917:Thrombin
D007527:Isoenzymes; D019007:P-Selectin; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D013917:Thrombin