Inhibition of epidermal growth factor binding to mouse cultured cells by fibroblast-derived growth factor. Evidence for an indirect mechanism.
Fibroblast-derived growth factor (FDGF), a basic, heat- and acid-stable polypeptide partially purified from the serum-free conditioned medium of BHK cells transformed by simian virus 40, is a potent mitogen for Swiss 3T3 cells and causes a marked reduction in 125I-labeled epidermal growth factor (125I-EGF) binding to these cells. The activity which inhibits EGF binding coelutes with the growth-stimulating activity after gel filtration, ion exchange chromatography, and sodium dodecyl sulfate polyacrylamide gel electrophoresis. Both cellular responses are elicited by the same range of FDGF concentration in several murine cell types. The inhibition of EGF binding is rapid and results from a decrease in the apparent affinity of cellular receptors for 125I-EGF. FDGF does not affect the rate of cell-mediated 125I-EGF degradation. Several lines of evidence suggest that FDGF does not bind directly to EGF receptor. First, the effect of FDGF is dependent on the temperature of the assay; furthermore, treatment of cells with EGF results in loss of EGF receptors while exposure to FDGF for up to 24 h does not induce "down-regulation" of EGF receptors. Further, in A431 cells which display a large number of specific EGF receptors, 125I-EGF binding is not sensitive to FDGF. Finally, the effect of FDGF on 125I-EGF binding is not observed with isolated plasma membranes. Taken together, these findings suggest that FDGF binds to sites which are separate from EGF receptors. The results show a novel mechanism whereby a growth-promoting factor produced by a tumor cell line can rapidly modulate the affinity of the cellular receptors for EGF in an indirect manner.
D000818:Animals; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D004815:Epidermal Growth Factor / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D066246:ErbB Receptors; D005346:Fibroblast Growth Factors; D006133:Growth Substances / Q000494:pharmacology*; D051379:Mice; D010455:Peptides / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*
D006133:Growth Substances; D010455:Peptides; D011956:Receptors, Cell Surface; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D066246:ErbB Receptors