Regulation of epidermal growth factor (EGF) receptor activity during the modulation of protein synthesis.
The capacity of cultured human fibroblasts to bind 125I-labeled epidermal growth factor (EGF) was measured during protein synthesis inhibition and reinitiation. Protein synthesis was inhibited by incubation of human fibroblasts in histidine-free medium supplemented with L-histidinol to produce a stringent amino acid starvation. Under these conditions 125 I-EGF binding activity decreased with a half-life of 14.5 hours. Protein synthesis could be rapidly reinitiated by the addition of L-histidine to human fibroblasts which had been preincubated in histidinol containing media for 36 to 48 hours. 125I-EGF binding activity rapidly increased upon the reinitiation of protein synthesis. In the presence of serum 100% of the original binding capacity was recovered ten hours after the reinitiation or protein synthesis, while 70% of the binding capacity was recovered in 12 hours in serum-free media. The recovery of 125I-EGF binding activity after the reinitiation of protein synthesis, was not blocked by the presence of Actinomycin D, indicating that the messenger RNA for the EGF receptor may accumulate during the period of histidinol-mediated inhibition of protein synthesis. The time course of recovery of 125I-EGF binding activity after the reinitiation of protein synthesis is very similar to that observed during the recovery of receptor activity following "down regulation" of EGF receptor activity. Recovery from down regulation, however, was markedly sensitive to Actinomycin D.
D000596:Amino Acids / Q000172:deficiency; D002478:Cells, Cultured; D003470:Culture Media; D004815:Epidermal Growth Factor / Q000378:metabolism*; D006639:Histidine / Q000378:metabolism; D006801:Humans; D010455:Peptides / Q000378:metabolism*; D014176:Protein Biosynthesis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012867:Skin / Q000166:cytology
D000596:Amino Acids; D003470:Culture Media; D010455:Peptides; D011956:Receptors, Cell Surface; D006639:Histidine; D004815:Epidermal Growth Factor