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 mu M) inhibited completely formation of inositol phosphates in human platelets induced by collagen or by cross-linking of the platelet low affinity Fc receptor, Fc 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 mu M) 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.