AGGREGATION OF THE HIGH-AFFINITY IGE RECEPTOR AND ENHANCED ACTIVITY OF P53 56(LYN) PROTEIN-TYROSINE KINASE/

Aggregation of the receptor with high affinity for IgE (Fc epsilon RI) on the surface of mast cells and basophils stimulates phosphorylation of protein tyrosines, a process in which p53/56(lyn) kinase has been implicated. We measured the association between Fc epsilon RI and the kinase, using chemical crosslinking to stabilize their interaction. In the rat basophilic leukemia mast cell line, 3-4%, and at most 20%, of Fc epsilon RI appear to be associated with the kinase prior to aggreg ation, even though there is an excess of total cell lyn kinase. Aggreg ating the Fc epsilon RI causes three to four times more of the kinase to associate with receptors, a process requiring a prior phosphorylati on step. In an in vitro assay, the lyn associated with the aggregated receptors becomes disproportionately more phosphorylated than would be predicted from the amount of lyn associated with the receptors. These and other data are consistent with a model in which aggregation of th e receptor leads to its transphosphorylation by constitutively associa ted lyn kinase. We propose that additional molecules of this kinase ar e thereby recruited and that this markedly enhances transphosphorylati on of tyrosine on the receptor and associated proteins, thereby initia ting a cascade of further biochemical changes. This model is also cons istent with data on receptors such as the clonotypic receptors on B an d T lymphocytes, which share structural and functional features with F c epsilon RI.