title: Wheat germ agglutinin and concanavalin A inhibit the response of human fibroblasts to peptide growth factors by a post-receptor mechanism.
abstract: The effect of plant lectins on amino acid uptake and DNA synthesis in cultured human skin fibroblasts stimulated by various peptide mitogens was studied. Wheat germ agglutinin (WGA), at a concentration of 5 micrograms/ml, which by itself had little effect on 3H-aminoisobutyric acid (AIB) uptake, markedly inhibited stimulation of 3H-AIB uptake by somatomedin-C, insulin, epidermal growth factor (EGF) and platelet-derived growth factor. This inhibition could not be overcome by increasing the concentration of peptide added. Neither WGA nor concanavalin A (Con A) significantly affected basal 3H-thymidine incorporation. However both lectins, at concentrations of 5-20 micrograms/ml, decreased EGF- and insulin-stimulated DNA synthesis while succinyl Con A, a divalent lectin derivative, did not. The inhibitory effects of lectins on mitogenic stimulation were reversed by alpha-methyl mannose (Con A) or N-acetylglucosamine (WGA), and were not due to a reduction in the binding of growth factors to their receptors. It is concluded that certain lectins noncompetitively inhibit the response of human fibroblasts to multiple peptide mitogens at the post-receptor level, possibly by interfering with lateral mobility and aggregation of mitogen-receptor complexes.
mesh_terms: D000117:Acetylglucosamine / Q000494:pharmacology; D000328:Adult; D000621:Aminoisobutyric Acids / Q000378:metabolism; D001665:Binding Sites; D003208:Concanavalin A / Q000031:analogs & derivatives / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D037102:Lectins / Q000494:pharmacology*; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012867:Skin / Q000166:cytology; D013997:Time Factors; D014909:Wheat Germ Agglutinins
chemical_list: D000621:Aminoisobutyric Acids; D006133:Growth Substances; D007328:Insulin; D037102:Lectins; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D014909:Wheat Germ Agglutinins; D003208:Concanavalin A; C100049:2-aminoisobutyric acid; C019558:succinylconcanavalin A; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D000117:Acetylglucosamine