Cell
ArticleA steady state model for analyzing the cellular binding, internalization and degradation of polypeptide ligands
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2020, Pharmacology and TherapeuticsCitation Excerpt :Wiley et al. first derived a series of steady-state rate equations that expressed the relationship between ligand-binding to cell surface receptor, mechanism of receptor complex [LR] endocytosis, and the overall kinetics of complex turnover (Wiley & Cunningham, 1981). The authors outlined a simple graphical method (named an In/Sur plot) for direct determination of the endocytic rate constant, ke, defined as the probability of an occupied cell-surface receptor to be internalized in 1 min at physiological temperature (37 °C) (Wiley & Cunningham, 1981; Wiley & Cunningham, 1982). Initially, the authors demonstrated the utility of the approach with an analysis of 125I-EGF binding and internalization in human fibroblasts, where they showed that as long as the surface level of bound EGF was near constant (steady-state) and a sufficient lag between ligand internalization and degradation exists, then the derived ke for EGF-EGFR complex is independent of total receptor occupancy (Wiley & Cunningham, 1982).
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2012, Biochimica et Biophysica Acta - General SubjectsCitation Excerpt :The kinetic parameters of holo-Tf/TfR binding and dissociation at the cell surface can be determined by combining radioactivity experiments with mathematical modeling. In order to describe the rate of binding of holo-Tf to TfR on the cell surface, Lodish and coworkers derived a mathematical model, which expanded upon previously described models for the epidermal growth factor and asialoglycoprotein receptors [96–97]. Fig. 6 depicts the kinetic parameters of the Tf trafficking pathway.
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2009, Molecular OncologyCitation Excerpt :The value of k3 is therefore not identifiable from such a dataset, and no conclusions could be made based on its value. Below, an experimental protocol for estimating ke will be discussed (Wiley and Cunningham, 1981, 1982). The final step of the modelling process, model validation, is to determine whether the model can predict rather than simply reflect system behaviour.