Phenylarsine oxide inhibits tyrosine phosphorylation of phospholipase Cγ2 in human platelets and phospholipase Cγ1 in NIH-3T3 fibroblasts

The sulphydryl reagent phenylarsine oxide (PAO) (1 μM) inhibited completely formation of inositol phosphates in human platelets induced by collagen or by cross-linking of the platelet low affinity Fc receptor, FcγRIIA, but did not alter the response to the G protein receptor agonist thrombin. PAO also inhibited completely tyrosine phosphorylation of PLCγ2 in collagen and FcγRIIA-stimulated cells, although tyrosine phosphorylation of other proteins including the tyrosine kinase syk was relatively unaffected. PAO (1 μM) also inhibited completely tyrosine phosphorylation of PLCγ1 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 FcγRIIA cross-linking activate platelets through a pathway distinct from that used by thrombin and suggest that PAO may be a selective inhibitor of PLCγ relative to PLC β isozymes.