title: Phosphoinositide metabolism triggered by wheat germ agglutinin in human platelets.
abstract: The lectin wheat germ agglutinin (WGA) has been shown to elicit platelet functional responses such as aggregation and release reaction as a consequence of binding several cell surface glycoproteins in platelets, whereas physiological activators act on their specific receptors. To examine the mechanism of WGA-induced platelet activation, we analyzed phosphoinositide metabolism triggered by this lectin. The binding of WGA to human platelets induced a rapid and dose-dependent surge in phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) hydrolysis, as monitored by an increase in [Ca2+]i and phosphatidic acid production. Furthermore, it similarly elicited the synthesis of PtdIns(3,4)P2, which is a major 3-phosphorylated phosphoinositide in platelets. This 3-phosphorylated lipid generation induced by WGA was very strong and did not appear to be a consequence of the classical PtdIns(4,5)P2 hydrolysis. WGA also induced a marked increase in the degree of tyrosine phosphorylation of proteins in platelets, and this increase was correlated with the phosphoinositide metabolism, i.e. PtdIns(4,5)P2 breakdown and PtdIns(3,4)P2 synthesis. The non-selective inhibitor of protein kinases, staurosporine, inhibited similarly both the increase in tyrosine phosphorylation of several platelet proteins and the phosphoinositide changes in a dose-dependent manner. These findings suggest that both PtdIns(4,5)P2 hydrolysis and PtdIns(3,4)P2 synthesis are related to protein-tyrosine phosphorylation in platelets stimulated with WGA.
authors.affiliation: Department of Laboratory Medicine, Yamanashi Medical College, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yatomi
authors.forename: Y
authors.initials: Y
authors.lastname: Ozaki
authors.forename: S
authors.initials: S
authors.lastname: Kume
mesh_terms: D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D005069:Evaluation Studies as Topic; D006801:Humans; D010716:Phosphatidylinositols / Q000097:blood*; D010766:Phosphorylation; D014909:Wheat Germ Agglutinins / Q000494:pharmacology*
chemical_list: D010716:Phosphatidylinositols; D014909:Wheat Germ Agglutinins