Epidermal growth factor receptor binding is not a simple one-step process

K. H. Mayo, M. Nunez, C. Burke, C. Starbuck, D. Lauffenburger, C. R. Savage

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

The binding kinetics of 125I-labeled mouse epidermal growth factor (EGF) to receptors on human fibroblast cells in monolayer culture were measured at 4 °C. Initial binding rates as a function of hormone concentration allowed estimation of simple two-state on-off rate constants of 1.2 x 106 M-1 s-1 and 4.9 x 10-3 s-1, respectively. These two-state parameters gave inadequate computer fits to long term kinetic and equilibrium-binding data, suggesting that an additional process(es) was occurring. Nonlinear equilibrium Scatchard plots and transient 'pseudo-Scatchard' plots taken at pre-equilibrium times support the idea that at least one other process is occurring during receptor binding. 125I-EGF-receptor dissociation kinetic plots were biphasic, yielding rate constants of 1.5 x 10-2 s-1 and 5.6 x 10-5 s-1 with the ratio of the two components changing with the time of initial incubation with 125I-EGF. Application of a ternary complex model which assumed complexation of the bound receptor with a cell surface interaction molecule gave satisfactory fits to all data.

Original languageEnglish (US)
Pages (from-to)17838-17844
Number of pages7
JournalJournal of Biological Chemistry
Volume264
Issue number30
StatePublished - 1989

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