IgE receptor signaling utilizes specialized membrane domains

Our recent studies have led to the hypothesis that signal transduction immediately following aggregation of the high affinity receptor for immunoglobulin E (Fc epsilon RI) on mast cells involves the association of this receptor with specialized domains of the plasma membrane. We have evidence that these membrane domains, which are characterized by their resistance to solubilization by non-ionic detergents, mediate phosphorylation of aggregated receptors by supplying a locally high concentration of active tyrosine kinase, Lyn. Membrane domain-mediated Fc epsilon RI activation points to a model for signal initiation that emphasizes selective protein-lipid interactions to facilitate functional coupling between proteins. This co-compartmentalization that depends on FceRI aggregation is a mechanism for signal regulation that is increasingly appreciated as relevant to signaling by other receptors.