An unusual mechanism for ligand antagonism

Science. 1998 Jul 24;281(5376):568-72. doi: 10.1126/science.281.5376.568.

Abstract

The ratio of late to early events stimulated by the mast cell receptor for immunoglobulin E (IgE) correlated with the affinity of a ligand for the receptor-bound IgE. Because excess receptors clustered by a weakly binding ligand could hoard a critical initiating kinase, they prevented the outnumbered clusters engendered by the high-affinity ligands from launching the more complete cascade. A similar mechanism could explain the antagonistic action of some peptides on the activation of T cells.

MeSH terms

  • 2,4-Dinitrophenol / immunology
  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antibody Affinity
  • Antigen-Antibody Reactions
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Dansyl Compounds
  • Enzyme Precursors / metabolism
  • Focal Adhesion Kinase 2
  • Haptens / immunology*
  • Haptens / metabolism
  • Immunoglobulin E / immunology
  • Immunoglobulin E / metabolism*
  • Intracellular Signaling Peptides and Proteins
  • Ligands
  • Mast Cells / immunology*
  • Mitogen-Activated Protein Kinase 1
  • Oncogene Proteins / metabolism
  • Phosphorylation
  • Phosphotyrosine / metabolism
  • Protein-Tyrosine Kinases / metabolism
  • Rats
  • Receptor Aggregation
  • Receptors, IgE / immunology
  • Receptors, IgE / metabolism*
  • Signal Transduction
  • Syk Kinase
  • T-Lymphocytes / immunology
  • Tumor Cells, Cultured

Substances

  • Adaptor Proteins, Signal Transducing
  • Dansyl Compounds
  • Enzyme Precursors
  • Haptens
  • Intracellular Signaling Peptides and Proteins
  • Ligands
  • Nck protein
  • Oncogene Proteins
  • Receptors, IgE
  • Phosphotyrosine
  • Immunoglobulin E
  • Protein-Tyrosine Kinases
  • Focal Adhesion Kinase 2
  • Ptk2b protein, rat
  • Syk Kinase
  • Syk protein, rat
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • 2,4-Dinitrophenol