INTRACLUSTER RESTRICTION OF FC RECEPTOR GAMMA-CHAIN TYROSINE PHOSPHORYLATION SUBVERTED BY A PROTEIN-TYROSINE-PHOSPHATASE INHIBITOR

This study shows that aggregation of U937 cell high affinity IgG Fc re ceptor (Fc gamma RI) results in the transient tyrosine phosphorylation of Fc gamma RI gamma-chain but not the phosphorylation of gamma-chain s associated with nonaggregated IgA Fc receptors (Fc alpha R) on the s ame cells. Thus, normally, tyrosine phosphorylation of gamma-chains is limited to FcR in aggregates, In contrast, aggregation of Fc gamma RI in the presence of vanadate induced the sustained tyrosine phosphoryl ation of Fc gamma RI gamma-chains and the rapid and extensive phosphor ylation of nonaggregated Fc alpha R gamma-chains and low affinity IgG Fc receptors (Fc gamma RII). This global phosphorylation of motifs on nonaggregated FcR was also detected upon aggregation of Fc alpha R or Fc gamma RII, which induced the phosphorylation of nonaggregated Fc ga mma RI gamma-chains. Vanadate prevented dephosphorylation of proteins and increased kinase activity in stimulated cells, Evidence failed to support alternative explanations such as acquisition of phospho-gamma through subunit exchange or a coalescence of nonaggregated with aggreg ated FcR, It is likely, therefore, that activated kinases interacted w ith nonaggregated FcR in stimulated cells. Pervanadate induced the tyr osine phosphorylation of gamma-chains in the absence of FcR crosslinki ng, indicating that the kinases could be activated by phosphatase inhi bition and could react with nonaggregated substrates. We conclude that under normal conditions there is a vanadate-sensitive mechanism that prevents tyrosine phosphorylation of nonaggregated FcR gamma-chain mot ifs in activated cells, restricting their phosphorylation to aggregate s.