Modulation of the epidermal growth factor receptor by brain-derived growth factor in Swiss mouse 3T3 cells.
Incubation of Swiss mouse 3T3 cells at 37 degrees C with bovine brain-derived growth factor (BDGF) decrease the cell surface 125I-EGF binding activity of these cells by 70-80%. This down-modulation of the EGF receptor by BDGF was time, temperature, and dose dependent. Scatchard plot analysis indicated that BDGF binding led to a selective decrease in the number of high-affinity EGF receptors. The BDGF-induced down-modulation of the EGF receptor was completely blocked by protamine, a potent inhibitor of receptor binding and mitogenic activities of BDGF. BDGF down-modulated the EGF receptor in phorbol myristic acetate (PMA)-pretreated cells, as well as in control cells. Furthermore, PMA-pretreated cells responded mitogenically to BDGF, whereas PMA itself failed to stimulate the mitogenic response of PMA-pretreated cells. This BDGF-induced down-modulation of the EGF receptor in PMA-desensitized cells suggests that BDGF down-regulates the EGF receptor by a mechanism distinct from that of PMA. Incubation of cells with compounds which are known to inhibit pinocytosis blocked the down-modulation induced either by BDGF or by platelet-derived growth factor (PDGF) but had no effect on the PMA-induced down-modulation. Incubation of cells with inhibitors of receptor recycling enhanced the BDGF-induced down-modulation of the EGF receptor. These results suggest that BDGF and PDGF induce down-modulation of the EGF receptor by increasing the internalization of cell surface high-affinity receptors and that the internalization process may not be required for down-modulation induced by PMA.
Huang
S S
SS
E.A. Doisy Department of Biochemistry, St. Louis University School of Medicine, Missouri 63104.
Lokeshwar
V B
VB
Huang
J S
JS
D000818:Animals; D001923:Brain Chemistry; D019208:Brain-Derived Neurotrophic Factor; D002417:Cattle; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism*; D006133:Growth Substances / Q000502:physiology*; D008744:Methylamines / Q000494:pharmacology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D006133:Growth Substances; D008744:Methylamines; D009419:Nerve Tissue Proteins; C019277:brain-derived growth factor; D002738:Chloroquine; D004247:DNA; C027451:methylamine; D066246:ErbB Receptors