One Lyn molecule is sufficient to initiate phosphorylation of aggregated high-affinity IgE receptors

• DOI: 10.1073/pnas.96.15.8615
• Publication Date: 2002-07-26T14:35:07Z
• Authors: Carla Wofsy; Becky M. Vonakis; Henry Metzger; Byron Goldstein
• Keywords: 0301 basic medicine; 0303 health sciences; Protein Conformation; Receptors, IgE; Models, Immunological; CHO Cells; Transfection; Clone Cells; 03 medical and health sciences; src-Family Kinases; Cricetinae; Animals; Phosphorylation; Phosphotyrosine

In response to antigenic stimuli, the multisubunit immune recognition receptors become aggregated and then phosphorylated on their cytoplasmic tyrosines. For the clonotypic receptors of B and T cells and for Fc receptors such as the high-affinity receptor for IgE (FcɛRI), a Src family kinase initiates this phosphorylation. We ask whether aggregation of the initiating kinase itself is required for signal transduction or whether, alternatively, a single associated kinase molecule can phosphorylate the receptors in an aggregate. We formulate the alternative molecular mechanisms mathematically and compare predictions with experimental findings on FcɛRI-bearing cells expressing varying amounts of the transfected Src family kinase Lyn. The data are consistent with the requirement of only a single Lyn molecule per FcɛRI aggregate to initiate signaling and are inconsistent with a mechanism requiring more than one Lyn molecule.