Modeling the early signaling events mediated by FcepsilonRI.
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.
Goldstein
Byron
B
Theoretical Biology and Biophysics Group, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA. bxg@lanl.gov
Faeder
James R
JR
Hlavacek
William S
WS
Blinov
Michael L
ML
Redondo
Antonio
A
Wofsy
Carla
C
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
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