Glucocorticoid-mediated alteration in growth factor binding and action: Analysis of the binding change

✍ Scribed by Baker, Joffre B. ;Cunningham, Dennis D.

• Book ID: 102926549
• Publisher: Wiley (John Wiley & Sons)
• Year: 1978
• Tongue: English
• Weight: 591 KB
• Volume: 9
• Category: Article
• ISSN: 0091-7419
• DOI: 10.1002/jss.400090108

✦ Synopsis

The addition of the glucocorticoid analog dexamethasone (DX) t o serum-free cultures of human fibroblasts caused a twofold enhancement of the mitogenic response t o epidermal growth factor (EGF), although DX by itself was not mitogenic. A basis for this effect was suggested by studies showing that DX also increased the cellular binding of 125 I-EGF. DX increased the ability of the cells t o bind 12' I-EGF only at low physiological concentrations of this polypeptide. Thus, data from 12' I-EGF binding t o cells incubated without DX produced a linear Scatchard plot, whereas the data from 125 I-EGF binding t o DX-treated cells led t o an upwardly curvilinear Scatchard plot. Measurements of lZ5I-EGF association with the cell surface and cytoplasm indicated that this binding change involved an alteration of cell surface EGF receptors. The binding change appeared not t o involve negatively cooperative interactions between EGF receptors, nor a change in the number of receptors. The binding alteration could be explained by a model in which DX converted 25-30% of the cell surface EGF receptors to a form having a fourfold increased affinity.