Thrombin stimulates the production of a novel polyphosphoinositide in human platelets.
The sequential actions of phosphoinositide 4-kinase and 5-kinase and hydrolysis of phosphatidylinositol (PtdIns) 4,5-P2 are stimulated during platelet activation. Recently, a phosphoinositide 3-kinase has been implicated in signal transduction in several cell types. Stimulation of PtdIns(3,4)P2 synthesis has been shown in polyoma middle T-transformed and platelet-derived growth factor-stimulated cells, and this novel lipid has been implicated in signal transduction and regulation of cell proliferation. We demonstrate the formation of PtdIns(3,4)P2 in human platelets and show that the synthesis of this lipid (and of PtdIns(4,5)P2) is stimulated during activation of platelets by thrombin. This indicates the presence of phosphoinositide 3-kinase activity in platelets. We postulate that PtdIns(3,4)P2 is involved in signal transduction in platelets and discuss the possibility that this novel lipid is a substrate for phospholipase C.
Nolan
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Division of Cell Biology, Burroughs Wellcome Co., Research Triangle Park, North Carolina 27709.
Lapetina
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D000255:Adenosine Triphosphate / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000097:blood* / Q000302:isolation & purification; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000097:blood* / Q000302:isolation & purification; D010761:Phosphorus Radioisotopes; D011865:Radioisotope Dilution Technique; D015398:Signal Transduction; D013917:Thrombin / Q000502:physiology*; D014316:Tritium
D007295:Inositol Phosphates; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D010761:Phosphorus Radioisotopes; D014316:Tritium; D000255:Adenosine Triphosphate; D013917:Thrombin