title: Modeling the early signaling events mediated by FcepsilonRI.
abstract: We present a detailed mathematical model of the phosphorylation and dephosphorylation events that occur upon ligand-induced receptor aggregation, for a transfectant expressing FcepsilonRI, Lyn, Syk and endogenous phosphatases that dephosphorylate exposed phosphotyrosines on FcepsilonRI and Syk. Through model simulations we show how changing the ligand concentration, and consequently the concentration of receptor aggregates, can change the nature of a cellular response as well as its amplitude. We illustrate the value of the model in analyzing experimental data by using it to show that the intrinsic rate of dephosphorylation of the FcepsilonRI gamma immunoreceptor tyrosine-based activation motif (ITAM) in rat basophilic leukemia (RBL) cells is much faster than the observed rate, provided that all of the cytosolic Syk is available to receptors.
authors.affiliation: Theoretical Biology and Biophysics Group, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA. bxg@lanl.gov
authors.forename: Byron
authors.initials: B
authors.lastname: Goldstein
authors.forename: James R
authors.initials: JR
authors.lastname: Faeder
authors.forename: William S
authors.initials: WS
authors.lastname: Hlavacek
authors.forename: Michael L
authors.initials: ML
authors.lastname: Blinov
authors.forename: Antonio
authors.initials: A
authors.lastname: Redondo
authors.forename: Carla
authors.initials: C
authors.lastname: Wofsy
mesh_terms: D000818:Animals; D001491:Basophils / Q000201:enzymology / Q000276:immunology; D016466:CHO Cells; D006224:Cricetinae; D004792:Enzyme Precursors / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D008024:Ligands; D008962:Models, Theoretical; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D017455:Receptors, IgE / Q000378:metabolism*; D015398:Signal Transduction; D000072377:Syk Kinase; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D017455:Receptors, IgE; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606898:Syk protein, rat; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases