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

Effects of epidermal growth factor and 12-O-tetradecanoylphorbol-13-acetate on metabolism of the epidermal growth factor receptor in normal human fibroblasts
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表皮生长因子和12-O-十四烷酰佛波醇-13-乙酸酯对正常人成纤维细胞表皮生长因子受体代谢的影响

DOI:
--
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发表时间:
1984
影响因子:
5.3
通讯作者:
S. Decker
S. Decker
中科院分区:
生物学2区
文献类型:
--
作者:
S. Decker

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检测了正常人成纤维细胞中表皮生长因子(EGF)受体的生物合成、磷酸化和降解。该受体最初被合成为MR=160,000的未成熟形式,然后以莫能菌素敏感的方式成熟为MR=170,000形式。衣霉素处理导致蛋白质的积累,mR=130,000。在正常生长和静止的细胞中,受体在丝氨酸和苏氨酸残基上被磷酸化,用EGF或肿瘤促进剂12-O-十四酰佛波醇-13-乙酸酯(TPA)处理后,受体结合的磷酸盐增加了两到三倍。EGF增加了磷酸丝氨酸和磷酸苏氨酸的含量,并导致少量磷酸酪氨酸的出现。TPA可使磷酸丝氨酸和磷酸苏氨酸水平明显升高。预先用TPA处理可抑制受体中依赖于EGF的磷酸酪氨酸的出现。对胰酶磷酸肽的分析表明,七个主要多肽中有六个是EGF或TPA处理的细胞中的受体共有的。EGF强烈刺激融合细胞的[~3H]胸腺嘧啶核苷掺入,使最终饱和密度增加三到四倍,并使整个细胞的磷酸酪氨酸水平增加约三倍。在加入EGF之前用TPA处理细胞可以抑制所有这三种EGF依赖的反应。EGF还可使受体半衰期从15h缩短至1h,但TPA不能抑制这一作用。TPA单独对受体半衰期无明显影响。
The biosynthesis, phosphorylation, and degradation of the epidermal growth factor (EGF) receptor were examined in normal human fibroblasts. The receptor was initially synthesized as an Mr = 160,000 immature form which matured to an Mr = 170,000 form in a monensin-sensitive manner. Tunicamycin treatment led to the accumulation of an Mr = 130,000 protein. The receptor was phosphorylated on serine and threonine residues in normally growing and quiescent cells, and treatment with EGF or the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in a two- to threefold increase in receptor-bound phosphate. EGF increased the amount of phosphoserine and phosphothreonine and caused the appearance of a minor amount of phosphotyrosine. TPA increased the levels of phosphoserine and phosphothreonine exclusively. Prior treatment with TPA inhibited the EGF-dependent appearance of phosphotyrosine in the receptor. Analysis of tryptic phosphopeptides revealed that six of the seven major peptides were common to the receptor from cells treated with EGF or TPA. EGF strongly stimulated [3H]thymidine incorporation in confluent cells, increased final saturation density three to fourfold, and increased whole-cell levels of phosphotyrosine about threefold. Treatment of cells with TPA before addition of EGF inhibited all three of these EGF-dependent responses. EGF also decreased the receptor half-life from 15 h to 1 h, but this was not inhibited by TPA. TPA alone had no detectable effect on the receptor half-life.
血小板源性生长因子和胆原对表皮生长因子受体的调节:对有丝分裂的影响。
DOI: 10.1073/pnas.79.18.5567
发表时间: 1982
影响因子: 11.1
作者:
Wharton,W;Leof,E;Pledger,WJ;O'Keefe,EJ
通讯作者: O'Keefe,EJ
人乳腺癌细胞中表皮生长因子和佛波酯肿瘤促进剂之间的拮抗作用。
DOI: 10.1172/jci110144
发表时间: 1981
期刊: The Journal of clinical investigation
影响因子: --
作者:
Osborne,CK;Hamilton,B;Nover,M;Ziegler,J
通讯作者: Ziegler,J
EGF 受体激酶具有多个磷酸化位点。
DOI: 10.1016/s0006-291x(82)80010-7
发表时间: 1982
影响因子: 3.1
作者:
Gates,RE;KingJr,LE
通讯作者: KingJr,LE
表皮生长因子-受体-蛋白激酶相互作用。
DOI: --
发表时间: 1981
期刊: Progress in clinical and biological research
影响因子: --
作者:
Cohen,S;Carpenter,G;KingJr,L
通讯作者: KingJr,L