Protein kinase C-mediated formation of phosphatidylinositol 3,4-bisphosphate in human platelets.
The effect of phorbol 12,13-dibutyrate on the formation of phosphatidylinositol 3,4-bisphosphate in washed human platelets was studied. Platelets labelled with [32P]Pi were stimulated with phorbol 12,13-dibutyrate or thrombin in the presence or absence of staurosporine. Lipids were extracted, and deacylated, and the glycerophosphoinositol derivatives were analyzed by high performance liquid chromatography. Phorbol 12,13-dibutyrate increased formation of phosphatidylinositol 4-monophosphate and phosphatidylinositol 3,4-bisphosphate in a dose- and time-dependent manner. Thrombin also increased formation of phosphatidylinositol 3,4-bisphosphate. Staurosporine completely inhibited phorbol 12,13-dibutyrate or thrombin-stimulated production of phosphatidylinositol 3,4-bisphosphate. These data indicate that production of phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 4-monophosphate is mediated by protein kinase C. It is widely recognized that production of phosphatidylinositol 3,4-bisphosphate is caused by the tyrosine kinase-mediated activation of phosphatidylinositol 3-kinase. However, in platelets, production of phosphatidylinositol 3,4-bisphosphate might be related to stimulation of phosphatidylinositol 4-kinase, which is activated by protein kinase C.
Yamamoto
K
K
Division of Cell Biology, Burroughs Wellcome Co., Research Triangle Park, NC 27709.
Lapetina
E G
EG
D000470:Alkaloids / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004789:Enzyme Activation; D006801:Humans; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000378:metabolism*; D011493:Protein Kinase C / Q000494:pharmacology*; D019311:Staurosporine; D013917:Thrombin / Q000494:pharmacology
D000470:Alkaloids; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; C060980:phosphatidylinositol 3,4-diphosphate; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D013917:Thrombin; D019311:Staurosporine