Aggregation of the high-affinity IgE receptor and enhanced activity of p53/56lyn protein-tyrosine kinase.
Aggregation of the receptor with high affinity for IgE (Fc epsilon RI) on the surface of mast cells and basophils stimulates phosphorylation of protein tyrosines, a process in which p53/56lyn kinase has been implicated. We measured the association between Fc epsilon RI and the kinase, using chemical crosslinking to stabilize their interaction. In the rat basophilic leukemia mast cell line, 3-4%, and at most 20%, of Fc epsilon RI appear to be associated with the kinase prior to aggregation, even though there is an excess of total cell lyn kinase. Aggregating the Fc epsilon RI causes three to four times more of the kinase to associate with receptors, a process requiring a prior phosphorylation step. In an in vitro assay, the lyn associated with the aggregated receptors becomes disproportionately more phosphorylated than would be predicted from the amount of lyn associated with the receptors. These and other data are consistent with a model in which aggregation of the receptor leads to its transphosphorylation by constitutively associated lyn kinase. We propose that additional molecules of this kinase are thereby recruited and that this markedly enhances transphosphorylation of tyrosine on the receptor and associated proteins, thereby initiating a cascade of further biochemical changes. This model is also consistent with data on receptors such as the clonotypic receptors on B and T lymphocytes, which share structural and functional features with Fc epsilon RI.
Yamashita
T
T
Section on Chemical Immunology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-1820.
Mao
S Y
SY
Metzger
H
H
D000818:Animals; D003432:Cross-Linking Reagents; D004789:Enzyme Activation; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008407:Mast Cells / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D011940:Receptor Aggregation; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D017455:Receptors, IgE / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D019061:src-Family Kinases
D003432:Cross-Linking Reagents; D046911:Macromolecular Substances; D017455:Receptors, IgE; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases