EFFECT OF GENISTEIN, A TYROSINE KINASE INHIBITOR, ON U46619-INDUCED PHOSPHOINOSITIDE PHOSPHORYLATION IN HUMAN PLATELETS

Recent evidence suggests that the agonist-induced formation of phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2) via PI and PIP kinases may play an important role in transmembrane signalling. In the present work, the effect of genistein, a specific inhibitor of protein-tyrosine kinase, on phosphoinositide phosophorylation was studied in human platelets stimulated with the endoperoxide analogue, U46619. At 100μM concentration, genistein, but not the related compounds, flavone and biochanin A, which possess only weak anti-protein-tyrosine kinase activity, significantly inhibited the U46619-induced accumulation of [3H]PIP (by 71%) and [3H]PIP2. These data suggest that phosphoinositide phosphorylation may be regulated, in part, by tyrosine phosphorylation in U46619-stimulated platelets. © 1990.