Epidermal growth factor-induced stimulation of epidermal growth factor-receptor synthesis in human cytotrophoblasts and A431 carcinoma cells.
Epidermal growth factor (EGF)-receptor is a transmembrane glycoprotein whose intracellular degradation is known to be enhanced by EGF. We tested whether the receptor is replenished during this process by an enhanced rate of synthesis. Human A431 epidermoid carcinoma cells and primary cultures of human placental cytotrophoblasts were used in these studies. Cells were labeled with [35S]methionine, and EGF-receptor biosynthesis was quantitated by immunoprecipitation using a monoclonal anti-EGF-receptor antibody. EGF stimulated receptor biosynthesis at concentrations of 0.1 to 1 nM. The effect was seen within 2 h of EGF addition. At high EGF concentrations the stimulatory effect was diminished. In contrast, the effect of EGF on receptor degradation in these cells was negligible at low nanomolar concentrations and was pronounced only at saturating concentrations (greater than or equal to 10 nM). These results show that occupation of the cell surface EGF-receptor by its ligand can lead to the production of more receptor protein, thus counterbalancing the negative effect on receptor degradation. At low nanomolar concentrations of EGF the stimulatory effect on receptor synthesis predominates over degradation, indicating a positive regulatory role of EGF in receptor action.
DePalo
L
L
Department of Biochemistry and Biophysics, University of Pennsylvania, School of Medicine, Philadelphia 19104.
Das
M
M
D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000187:drug effects; D006801:Humans; D013268:Stimulation, Chemical; D014327:Trophoblasts / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D004815:Epidermal Growth Factor; D066246:ErbB Receptors