Phenylarsine oxide inhibits tyrosine phosphorylation of phospholipase C gamma 2 in human platelets and phospholipase C gamma 1 in NIH-3T3 fibroblasts.
The sulphydryl reagent phenylarsine oxide (PAO) (1 microM) inhibited completely formation of inositol phosphates in human platelets induced by collagen or by cross-linking of the platelet low affinity Fc receptor, F c gamma RIIA, but did not alter the response to the G protein receptor agonist thrombin. PAO also inhibited completely tyrosine phosphorylation of PLC gamma 2 in collagen and Fc gamma RIIA-stimulated cells, although tyrosine phosphorylation of other proteins including the tyrosine kinase syk was relatively unaffected. PAO (1 microM) also inhibited completely tyrosine phosphorylation of PLC gamma 1 induced by platelet derived growth factor (PDGF) in NIH-3T3 fibroblasts but only partially reduced phosphorylation of the PDGF receptor. These results provide further evidence that collagen and Fc gamma RIIA cross-linking activate platelets through a pathway distinct from that used by thrombin and suggest that PAO may be a selective inhibitor of PLC gamma relative to PLC beta isozymes.
Yanaga
F
F
University Department of Pharmacology, Oxford, UK.
Asselin
J
J
Schieven
G L
GL
Watson
S P
SP
D016475:3T3 Cells; D000818:Animals; D015703:Antigens, CD; D001152:Arsenicals / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D003094:Collagen / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D007295:Inositol Phosphates / Q000096:biosynthesis; D007527:Isoenzymes / Q000378:metabolism*; D051379:Mice; D051966:Phospholipase C gamma; D010766:Phosphorylation / Q000187:drug effects; D015539:Platelet Activation / Q000187:drug effects*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D017452:Receptors, IgG / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D015703:Antigens, CD; D001152:Arsenicals; D004791:Enzyme Inhibitors; C080568:Fc gamma receptor IIA; D007295:Inositol Phosphates; D007527:Isoenzymes; D010982:Platelet-Derived Growth Factor; D017452:Receptors, IgG; C029341:oxophenylarsine; D014443:Tyrosine; D003094:Collagen; D010738:Type C Phospholipases; D051966:Phospholipase C gamma