Compartmentalized Activation of the High Affinity Immunoglobulin E Receptor within Membrane Domains*
- ‡ To whom correspondence may be addressed. Tel.: 607-255-4095; Fax: 607-255-4137; E-mail: bab13{at}cornell.edu.
Abstract
The earliest known step in the activation of the high affinity IgE receptor, FcϵRI, is the tyrosine phosphorylation of its β and γ subunits by the Src family tyrosine kinase, Lyn. We report here that aggregation-dependent association of FcϵRI with specialized regions of the plasma membrane precedes its tyrosine phosphorylation and appears necessary for this event. Tyrosine phosphorylation of β and γ occurs in intact cells only for FcϵRI that associate with these detergent-resistant membrane domains, which are enriched in active Lyn. Furthermore, efficient in vitro tyrosine phosphorylation of FcϵRI subunits occurs only for those associated with isolated domains. This association and in vitro phosphorylation are highly sensitive to low concentrations of detergent, suggesting that lipid-mediated interactions with Lyn are important in FcϵRI activation. Participation of membrane domains accounts for previously unexplained aspects of FcϵRI-mediated signaling and may be relevant to signaling by other multichain immune receptors.
Footnotes
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↵* This work was supported by Grants AI22449 and GM07273 (to K. A. F.) from the National Institutes of Health. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 The abbreviations used are:
- RBL
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rat basophilic leukemia
- DNP
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dinitrophenyl.
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↵2 K. A. Field, D. Holowka, and B. Baird, unpublished observations.
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↵3 K. A. Field, D. Holowka, and B. Baird, manuscript in preparation.
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↵4 S. M. Schuh and D. L. Lublin, personal communication.
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- Received September 24, 1996.
- Revision received December 3, 1996.
- © 1997 by The American Society for Biochemistry and Molecular Biology, Inc.
