Detergent-resistant microdomains offer no refuge for proteins phosphorylated by the IgE receptor.

When the high affinity receptor for IgE and related receptors become aggregated, they emigrate to specialized microdomains of the plasma membrane that are enriched in certain lipids and lipid-anchored proteins. Among the latter are the kinases that initiate signaling cascade(s) by phosphorylating the receptors. In studying the IgE receptor, we explored whether, in addition to their potential role in enhancing the initiation of signaling by the kinase(s), the microdomains might augment the stimulation by excluding phosphatases. In vitro assessment of phosphatase activity, using either a relevant or irrelevant substrate, suggested that the microdomains were deficient in phosphatase activity, but, in vivo, proteins confined to the microdomains were found to be no less vulnerable to dephosphorylation than those outside such domains. In the course of our experiments, we observed that the procedures routinely used to isolate the detergent-resistant domains dissociated the receptor for IgE, thereby artificially accentuating the observed preferential distribution of phosphorylated subunits in the microdomains.