The Fc(epsilon)RIbeta subunit functions as an amplifier of Fc(epsilon)RIgamma-mediated cell activation signals.
The high affinity IgE receptor (Fc(epsilon)RI) plays a central role in the initiation of allergic responses. Fc(epsilon)RI is multimeric and is expressed as either (alpha)(gamma2) trimers or (alpha)(beta)(gamma2) tetramers. Recently, polymorphisms of the beta chain gene have been associated with the development of various allergic phenotypes. Until now, the role of beta in Fc(epsilon)RI-dependent signaling was largely unknown. For that reason, we compared the signaling characteristics of various wild-type and mutant (alpha)(gamma2) and (alpha)(beta)(gamma2) Fc(epsilon)RI complexes. These studies demonstrate that the gamma dimer functions as an autonomous activation module, while beta functions as an amplifier that provides a gain of 5- to 7-fold, as measured by Syk activation and calcium mobilization.
Lin
S
S
Laboratory of Allergy and Immunology, Department of Pathology, Beth Isreal Hospital, Boston, Massachusetts 02215, USA.
Cicala
C
C
Scharenberg
A M
AM
Kinet
J P
JP
D002118:Calcium / Q000378:metabolism; D002460:Cell Line / Q000276:immunology; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D004792:Enzyme Precursors / Q000378:metabolism; D006410:Hematopoiesis / Q000276:immunology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000201:enzymology / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins; D015473:Leukemia, Promyelocytic, Acute; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D009154:Mutation / Q000276:immunology; D010766:Phosphorylation; D011110:Polymorphism, Genetic; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D000072377:Syk Kinase; D014407:Tumor Cells, Cultured / Q000276:immunology; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D017455:Receptors, IgE; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D002118:Calcium