pH sensitivity of epidermal growth factor receptor complexes.
The association/dissociation binding kinetics of 125I-labeled mouse epidermal growth factor (EGF) to receptors on human fibroblast cells in monolayer culture have been measured at 4 degrees C as a function of extracellular pH from pH 5-9. At pH 8, steady-state total binding is maximal. As pH is lowered to 6.5, total binding monotonically decreases dramatically. It changes further only slightly between pH 6.5 and 5 to about 20% of the maximum binding value. Scatchard binding plots at pH 7.5 and above show the commonly observed concave-upward, non-linear curve; as pH is lowered, this plot becomes much more linear, indicating that the "high affinity" bound receptor population is greatly diminished. Application of our ternary complex binding model [Mayo et al., J Biol Chem 264:17838-17844, 1989], which hypothesizes complexation of the EGF-bound receptor with a cell surface interaction molecule, indicates that pH may have some direct effects on ternary complex formation, but the major effect is on EGF-receptor dissociation.
Jefferson Cancer Institute, Department of Pharmacology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
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D066246:ErbB Receptors / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008956:Models, Chemical; D011869:Radioligand Assay
D066246:ErbB Receptors