Effects of epidermal growth factor and 12-O-tetradecanoylphorbol-13-acetate on metabolism of the epidermal growth factor receptor in normal human fibroblasts.

摘要: The biosynthesis, phosphorylation, and degradation of the epidermal growth factor (EGF) receptor were examined in normal human fibroblasts. was initially synthesized as an Mr = 160,000 immature form which matured to 170,000 a monensin-sensitive manner. Tunicamycin treatment led accumulation 130,000 protein. phosphorylated on serine threonine residues normally growing quiescent cells, with EGF or tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted two- threefold increase receptor-bound phosphate. increased amount phosphoserine phosphothreonine caused appearance minor phosphotyrosine. TPA levels exclusively. Prior inhibited EGF-dependent phosphotyrosine receptor. Analysis tryptic phosphopeptides revealed that six seven major peptides common from cells treated TPA. strongly stimulated [3H]thymidine incorporation confluent final saturation density three fourfold, whole-cell about threefold. Treatment before addition all these responses. also decreased half-life 15 h 1 h, but this not by alone had no detectable effect half-life.