Total inhibition of phospholipase C and phosphatidylinositol 3-kinase by okadaic acid in thrombin-stimulated platelets.
Cell Signal
; 9(1): 117-24, 1997 Jan.
Article
em En
| MEDLINE
| ID: mdl-9067640
ABSTRACT
The strong inhibition of thrombin-induced platelet functions induced by okadaic acid is not correlated with the partial modification of pleckstrin phosphorylation, which remains still phosphorylated two min after stimulation, indicating that protein kinase C is not affected by okadaic acid. We then investigated the effect of okadaic acid on platelet lipid metabolism. Our data indicate that inhibition indeed strongly affects phosphatidic acid as well as phosphatidylinositol 3,4-bisphosphate synthesis at low concentrations of okadaic acid, and phosphatidylinositol 4,5-bisphosphate at higher concentrations. Since thrombin-induced tyrosine phosphorylations were completely inhibited in the presence of okadaic acid, as a consequence, phosphatidylinositol 3-kinase was no longer detected in antiphosphotyrosine immunoprecipitates, thus explaining the absence of phosphatidylinositol, 3,4-bisphosphate synthesis. Finally, okadaic acid inhibited thrombin-induced fibrinogen binding, indicating that serine/threonine phosphatases may affect the inside-out signalling which regulates the alpha 11bb3 integrin, downstream protein kinase C activation.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfolipases Tipo C
/
Fosfoproteínas
/
Plaquetas
/
Trombina
/
Fosfotransferases (Aceptor do Grupo Álcool)
/
Ácido Okadáico
/
Inibidores Enzimáticos
/
Mitógenos
Limite:
Humans
Idioma:
En
Revista:
Cell Signal
Ano de publicação:
1997
Tipo de documento:
Article
País de afiliação:
França