Signal transduction by FcεRI: Analysis of the early molecular events

Henry Metzger, Huaxian Chen, Byron Goldstein, Hana Haleem-Smith, John Inman, Mathew Peirce, Chikako Torigoe, Becky Vonakis, Carla Wofsy

Research output: Contribution to journalReview article

Abstract

We are analysing the initial molecular events stimulated by the high- affinity receptor for IgE, FcεRI. Earlier studies have shown that the first response when the receptor-bound IgE interacts with a multivalent antigen is a transphosphorylation of receptor tyrosines, induced by the approximation of two or more receptors by a constitutively associated src-family kinase (Lyn). The amount of weakly associated kinase regulates the intensity of the response. Several aspects are being analyzed: (i) the sites on Lyn and the receptor that account for the constitutive interaction; (ii) how the intrinsic affinity of a ligand for the receptor-bound IgE influences the responses; and (iii) the mechanism(s) by which low-affinity ligands can act as antagonists. In the latter studies, mast cell responses were followed by monitoring the phosphorylation of tyrosines on several proteins and secretion. At equivalent levels of receptor phosphorylation, a ligand with high affinity stimulated vigorous phosphorylation of downstream components, whereas a low-affinity ligand was unable to stimulate phosphorylation of the same components effectively. Cells stimulated with a mixture of high- and low-affinity ligands, under a protocol where simple displacement of one by the other was prevented, remarkably showed that excess low-affinity ligand inhibited the phosphorylation as well as degranulation by the high-affinity ligand. This antagonism results from a competition for the limiting amount of the constitutive initiating kinase. Related receptors that depend on recruitment of initiating kinases may be subject to similar regulatory mechanisms.

Original languageEnglish (US)
Pages (from-to)161-169
Number of pages9
JournalAllergology International
Volume48
Issue number3
DOIs
StatePublished - Jan 1 1999

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Keywords

  • IgE receptor
  • Mast cells
  • Membrane receptors
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Immunology and Allergy

Cite this

Metzger, H., Chen, H., Goldstein, B., Haleem-Smith, H., Inman, J., Peirce, M., Torigoe, C., Vonakis, B., & Wofsy, C. (1999). Signal transduction by FcεRI: Analysis of the early molecular events. Allergology International, 48(3), 161-169. https://doi.org/10.1046/j.1440-1592.1999.00132.x