title: Activation of human platelets by peroxovanadate is associated with tyrosine phosphorylation of phospholipase C gamma and formation of inositol phosphates.
abstract: Vanadate ions in the presence of H2O2 (peroxovanadate) induce a marked increase in the degree of tyrosine phosphorylation of proteins in human platelets. This increase preceded the onset of platelet shape change and aggregation, and is associated with activation of phospholipase C and increased [32P]phosphorylation of proteins of 47 kDa, a substrate for protein kinase C, and 20 kDa, a substrate for both myosin light-chain kinase and protein kinase C. The non-selective inhibitor of protein kinases, staurosporine, inhibits the increase in tyrosine phosphorylation of nearly all proteins and inhibits completely all other functional responses, suggesting that these events may be linked. In support of this, peroxovanadate stimulates tyrosine phosphorylation of phospholipase C gamma 1, suggesting that this may underlie its mechanism of platelet activation. Staurosporine also inhibited activation of phospholipase C by collagen, suggesting that tyrosine phosphorylation has an important role in the early stages of collagen-induced platelet activation.
authors.affiliation: Department of Pharmacology, University of Oxford, U.K.
authors.forename: R A
authors.initials: RA
authors.lastname: Blake
authors.forename: T R
authors.initials: TR
authors.lastname: Walker
authors.forename: S P
authors.initials: SP
authors.lastname: Watson
mesh_terms: D004789:Enzyme Activation; D006801:Humans; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000096:biosynthesis*; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*; D014638:Vanadates / Q000494:pharmacology*
chemical_list: D007295:Inositol Phosphates; C069276:peroxovanadate; D014638:Vanadates; D014443:Tyrosine; D011493:Protein Kinase C; D010738:Type C Phospholipases