Modulation of the epidermal growth factor receptor by brain-derived growth factor in Swiss mouse 3T3 cells

✍ Scribed by Shuan Shian Huang; Vinata B. Lokeshwar; Jung San Huang

• Publisher: John Wiley and Sons
• Year: 1988
• Tongue: English
• Weight: 721 KB
• Volume: 36
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.240360303

✦ Synopsis

Incubation of Swiss mouse 3T3 cells at 37°C with bovine brain-derived growth factor (BDGF) decreased the cell surface '251-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 downregulates 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 BDGFinduced 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.