Antigen-mediated IGE receptor aggregation and signaling: a window on cell surface structure and dynamics.
The high-affinity receptor for immunoglobulin E, Fc epsilon RI, serves as an archtype for multisubunit immunoreceptors that mediate cell activation in response to foreign antigens. Antigen-mediated aggregation of this receptor at the surface of mast cells and basophils initiates a biochemical cascade that uses nonreceptor tyrosine kinases as key participants in the earliest steps of this signal transduction process. Cross-linking of Fc epsilon RI with ligands of well-defined structure and valency has revealed detailed information about the fundamental requirements for functionally active receptor aggregates. Cross-linking-dependent changes in the interaction of these receptors with other cellular components have been characterized with biochemical and biophysical methods to develop a more complete view of signal initiation. Recent evidence suggests that this process involves the interaction of aggregated Fc epsilon RI with specialized plasma membrane domains that may localize important signaling molecules in the vicinity of aggregated receptors. Although these various studies were aimed toward understanding the operation of one cell surface receptor, they provide new insights into plasma membrane structure and dynamics that are generally relevant to the function of most nucleated mammalian cells.
Holowka
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D
Department of Chemistry, Cornell University, Ithaca, New York 14853-1301, USA.
Baird
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B
D000595:Amino Acid Sequence; D000818:Animals; D001491:Basophils / Q000276:immunology; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003902:Detergents / Q000494:pharmacology; D004058:Diffusion; D007073:Immunoglobulin E / Q000276:immunology*; D007152:Immunologic Capping; D015471:Leukemia, Basophilic, Acute / Q000473:pathology; D008024:Ligands; D008407:Mast Cells / Q000276:immunology; D008565:Membrane Proteins / Q000737:chemistry / Q000276:immunology; D017830:Octoxynol / Q000494:pharmacology; D009842:Oligopeptides / Q000276:immunology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D051381:Rats; D017455:Receptors, IgE / Q000737:chemistry / Q000276:immunology*; D012399:Rotation; D015398:Signal Transduction / Q000502:physiology*; D014407:Tumor Cells, Cultured
D003902:Detergents; D008024:Ligands; D008565:Membrane Proteins; D009842:Oligopeptides; D017455:Receptors, IgE; C067808:N,N'-bis((epsilon-((2,4-dinitrophenyl)amino)caproyl)tyrosyl)cystine; D007073:Immunoglobulin E; D017830:Octoxynol; D011505:Protein-Tyrosine Kinases