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EGFR ligand‐mediated activation: insights from a quantitative study in mammalian membranes
Author(s) -
Li Edwin,
Placone Jesse,
Hristova Kalina
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.681.2
Subject(s) - phosphorylation , dimer , chemistry , membrane , ligand (biochemistry) , receptor , biophysics , kinase , signal transduction , microbiology and biotechnology , biochemistry , biology , organic chemistry
The activation of receptor tyrosine kinases occurs via lateral dimerization in the plasma membrane, which enables the cross‐phosphorylation of the two receptors in the dimer. Ligands are important regulators of this process, exerting their regulation by stabilizing the dimers. Activation is further regulated by various cellular processes which are not very well understood. A question arises if the complex process of RTK activation in mammalian membranes can be modeled, and predicted based on the laws of mass action, as a function of receptor and ligand concentration. Here we investigate whether this physicochemical approach is successful in describing the activation of EGFR in the presence of EGF and TGF‐α . We show that the apparent deactivation constants for EGF and TGF‐α are 1.08±0.33 x 10 3 nM 3 and 2.17±0.59 x 10 3 nM 3 , respectively. These are the first quantitative measurements of the potency of EGF and TGF‐α in EGFR activation, and are consistent with previous binding measurements. We further show that measurements of active receptor fraction are very well described by an apparent equilibrium between inactive monomers and active dimers, suggesting that a physicochemical description of ligand binding and phosphorylation is sufficient to describe and predict EGFR activation data based on Western blotting.