title: Dynamics of signal transduction after aggregation of cell-surface receptors: studies on the type I receptor for IgE.
abstract: Many ligands stimulate cellular responses by aggregating the cell-surface receptors to which they are bound. We investigated several mechanistic questions related to aggregation of receptors by using the high-affinity receptor for IgE (Fc epsilon RI) on mast cells as a model system. We briefly exposed cells to covalently cross-linked oligomers of IgE and then added excess monomeric IgE to prevent further aggregation. Early events were examined by monitoring the phosphorylation of protein tyrosines; later events were examined by monitoring secretion. We found that aggregated receptors continue to signal both late and early events in the absence of formation of new aggregates. Additional experiments suggested that the clustered receptors undergo a dynamic process of phosphorylation and dephosphorylation. Our findings suggest that for these and related receptors that function by aggregation, the persistence of signal transduction is directly related to the intrinsic affinity of the ligand for the individual receptor.
authors.affiliation: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: U M
authors.initials: UM
authors.lastname: Kent
authors.forename: S Y
authors.initials: SY
authors.lastname: Mao
authors.forename: C
authors.initials: C
authors.lastname: Wofsy
authors.forename: B
authors.initials: B
authors.lastname: Goldstein
authors.forename: S
authors.initials: S
authors.lastname: Ross
authors.forename: H
authors.initials: H
authors.lastname: Metzger
mesh_terms: D000818:Animals; D002463:Cell Membrane Permeability; D004492:Edetic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D011940:Receptor Aggregation; D017455:Receptors, IgE / Q000502:physiology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
chemical_list: D017455:Receptors, IgE; D019000:Phosphotyrosine; D014443:Tyrosine; D004492:Edetic Acid; D011505:Protein-Tyrosine Kinases; D001619:beta-N-Acetylhexosaminidases