Shuttling of initiating kinase between discrete aggregates of the high affinity receptor for IgE regulates the cellular response.
Using defined oligomers of IgE, our group previously studied the quantitative relationship between the aggregation of the high affinity receptors for IgE (Fc epsilonRI) and the earliest signals initiated by such aggregation: the phosphorylation of tyrosines on the receptor. Notably, at certain doses of the oligomers such phosphorylation reached a plateau level well before the aggregation of the receptors had reached a maximum. These findings and others led us to propose that aggregates of the receptor were competing for a limited amount of the critical kinase-thought to be Lyn in this system. This paper describes a test of this proposal. We incubated cells with two distinguishable IgEs and examined the effect of aggregating one or the other or both types on the phosphorylation. When receptors binding antigen-specific IgE were aggregated with polyvalent antigen, they became rapidly phosphorylated as expected. Remarkably, however, Fc epsilonRI that had already been phosphorylated by the binding of dimers of IgE, became dephosphorylated simultaneously. Furthermore, when the antigen-driven aggregates were dissociated with hapten, the phosphorylation pattern reverted to that seen prior to the addition of antigen: as the antigen-driven aggregates became dephosphorylated, the receptors stably aggregated by the bound oligomers became rapidly rephosphorylated. Dephosphorylation of oligomer-driven aggregates was also partially reversed during the "spontaneous" dephosphorylation of the antigen-driven receptors seen at longer times after addition of antigen. Thus signal transduction in this system is in part regulated by the shuttling of limited amounts of the kinase that initiates the cascade of phosphorylations.
Torigoe
C
C
The Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Goldstein
B
B
Wofsy
C
C
Metzger
H
H
D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D007073:Immunoglobulin E / Q000378:metabolism*; D008407:Mast Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D051381:Rats; D011940:Receptor Aggregation; D017455:Receptors, IgE / Q000378:metabolism*; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism*
D017455:Receptors, IgE; D007073:Immunoglobulin E; D019061:src-Family Kinases