A novel inhibitory action of wheat germ agglutinin on phospholipase C in HEL and MEG-01 cell lines.
Stimulation of HEL megakaryocytic cells by Fc gammaRIIA crosslinking is associated with tyrosine phosphorylation of syk and phospholipase C gamma2 (PLCgamma2) and is accompanied by formation of inositol phosphates and release of intracellular Ca2+. These responses are inhibited by the kinase inhibitors, staurosporine and ST271. In contrast, the G-protein receptor agonist, thrombin induces formation of inositol phosphates and release of intracellular calcium without an increase in tyrosine phosphorylation. The plant lectin wheat germ agglutinin (WGA) stimulates tyrosine phosphorylation of syk and PLCgamma2 but surprisingly does not stimulate formation of inositol phosphates and induce release of intracellular Ca2+. WGA also inhibited formation of inositol phosphates and release of intracellular Ca2+ by Fc gammaRIIA crosslinking and thrombin-stimulation. A similar inhibitory effect of WGA was observed against elevation of Ca2+ by the same two stimuli in MEG-01 megakaryotic cells. The results demonstrate a novel pathway of inhibition of PLC on crosslinking of cell surface proteins that is not present in platelets.
Rezaei
E
E
Department of Pharmacology, University of Oxford, UK.
Quek
L
L
Watson
S P
SP
D015703:Antigens, CD; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003432:Cross-Linking Reagents; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D017452:Receptors, IgG; D013917:Thrombin; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors*; D014909:Wheat Germ Agglutinins / Q000494:pharmacology*
D015703:Antigens, CD; D003432:Cross-Linking Reagents; C080568:Fc gamma receptor IIA; D007295:Inositol Phosphates; D017452:Receptors, IgG; D014909:Wheat Germ Agglutinins; D011505:Protein-Tyrosine Kinases; D010738:Type C Phospholipases; D013917:Thrombin; D002118:Calcium