Modeling the early signaling events mediated by FcepsilonRI

Mol Immunol. 2002 Sep;38(16-18):1213-9. doi: 10.1016/s0161-5890(02)00066-4.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Basophils / enzymology
  • Basophils / immunology
  • CHO Cells
  • Cricetinae
  • Enzyme Precursors / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Kinetics
  • Ligands
  • Models, Theoretical*
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism
  • Rats
  • Receptors, IgE / metabolism*
  • Signal Transduction*
  • Syk Kinase
  • Tumor Cells, Cultured
  • src-Family Kinases / metabolism

Substances

  • Enzyme Precursors
  • Intracellular Signaling Peptides and Proteins
  • Ligands
  • Receptors, IgE
  • Protein-Tyrosine Kinases
  • Syk Kinase
  • Syk protein, rat
  • lyn protein-tyrosine kinase
  • src-Family Kinases