Fc gamma receptor II stimulated formation of inositol phosphates in human platelets is blocked by tyrosine kinase inhibitors and associated with tyrosine phosphorylation of the receptor.
We report that activation of phospholipase C (PLC) by cross-linking of the platelet low-affinity Fc gamma receptor II (Fc gamma RII) is inhibited by two structurally distinct tyrosine kinase inhibitors, staurosporine and ST271. This contrasts with PLC activation induced by thrombin and U46619, a thromboxane mimetic, whose receptors have seven transmembrane domains characteristic of G-protein coupled receptors. Several proteins undergo phosphorylation on tyrosine on Fc gamma RII cross-linking upstream of protein kinase C (PKC), Ca2+ and aggregation, including the Fc gamma RII itself. The role of Fc gamma RII phosphorylation in the regulation of PLC is discussed.
Blake
R A
RA
Department of Biochemistry, University of Dundee, Scotland.
Asselin
J
J
Walker
T
T
Watson
S P
SP
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000470:Alkaloids / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007295:Inositol Phosphates / Q000097:blood*; D010766:Phosphorylation; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D017452:Receptors, IgG / Q000378:metabolism*; D019311:Staurosporine; D013343:Styrenes / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D000470:Alkaloids; D007211:Indoles; D007295:Inositol Phosphates; D011450:Prostaglandin Endoperoxides, Synthetic; D017452:Receptors, IgG; D013343:Styrenes; C086531:ST 271; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D014443:Tyrosine; D004533:Egtazic Acid; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D010738:Type C Phospholipases; D013917:Thrombin; D019311:Staurosporine; C064758:Ro 31-8220