Modeling the early signaling events mediated by FcεRI

被引:40
作者
Goldstein, B [1 ]
Faeder, JR
Hlavacek, WS
Blinov, ML
Redondo, A
Wofsy, C
机构
[1] Los Alamos Natl Lab, Theoret Biol & Biophys Grp, Div Theoret, Los Alamos, NM 87545 USA
[2] Weizmann Inst Sci, Fac Math & Comp Sci, IL-76100 Rehovot, Israel
[3] Los Alamos Natl Lab, Theoret Chem & Mol Phys Grp, Div Theoret, Los Alamos, NM 87545 USA
[4] Univ New Mexico, Dept Math & Stat, Albuquerque, NM 87131 USA
关键词
receptor aggregation; signal transduction; mathematical modeling; Fc epsilon RI; Lyn; Syk;
D O I
10.1016/S0161-5890(02)00066-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. Published by Elsevier Science Ltd.
引用
收藏
页码:1213 / 1219
页数:7
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