Epidermal growth factor and its receptor

Epidermal growth factor and its receptor
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表皮生长因子及其受体

DOI:
10.1016/0303-7207(87)90027-x
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发表时间:
1987
影响因子:
4.1
通讯作者:
J. B. Santon
J. B. Santon
中科院分区:
医学2区
文献类型:
--
作者:
G. Gill;P. Bertics;J. B. Santon

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表皮生长因子 (EGF) 以高亲和力和特异性与其跨膜受体外部域上的单个位点结合,以激活其细胞质部分的酪氨酸蛋白激酶活性。 EGF 受体基因在几种人类肿瘤中扩增并过度表达,表明原癌基因浓度增加会导致与癌基因 erb B 相似的组成型活性。EGF 受体的合成和降解受到调节,此外,磷酸化的共价修饰调节受体蛋白的活性。 Tyr1173 的分子内自磷酸化消除了竞争性抑制限制,增强了底物的磷酸化。 Thr654 被蛋白激酶 C 磷酸化会降低高亲和力 EGF 结合和 EGF 刺激的酪氨酸蛋白激酶活性,从而提供肿瘤启动子和其他配体·受体复合物异源调节 EGF 受体的机制。广泛的调节有助于正常的生长控制,取消调节控制会导致不受控制的生长,如人类肿瘤中的erbB转化和EGF受体基因扩增。
Epidermal growth factor (EGF) binds with high affinity and specificity to a single site on the external domain of its transmembrane receptor to activate the tyrosine protein kinase activity of its cytoplasmic portion. The EGF receptor gene is amplified and over-expressed in several human tumors, suggesting that increased concentrations of the proto-oncogene leads to constitutive activity similar to that seen with oncogene erb B. Synthesis and degradation of the EGF receptor are regulated, in addition, covalent modification by phosphorylation regulates activity of the receptor protein. Intramolecular self-phosphorylation of Tyr1173removes a competitive inhibitory constraint to enhance phosphorylation of substrates. Phosphorylation of Thr654by protein kinase C decreases high affinity EGF binding and EGF-stimulated tyrosine protein kinase activity, providing a mechanism for heterologous regulation of the EGF receptor by tumor promoters and other ligand · receptor complexes. Extensive regulation contributes to normal growth control, abrogation of regulatory controls contributes to uncontrolled growth as seen witherbBtransformation and EGF receptor gene amplification in human tumors.
DOI: --
发表时间: 1986-04
期刊: The Journal of biological chemistry
影响因子: --
作者:
H. S. Earp§V;K. Austin;Joyce BlaisdellSg;R. A. Rubin;Karen G NelsonII;Lester W. LeelJ;Joe W. GrishamSJJ
通讯作者: H. S. Earp§V;K. Austin;Joyce BlaisdellSg;R. A. Rubin;Karen G NelsonII;Lester W. LeelJ;Joe W. GrishamSJJ
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影响因子: --
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cAMP 依赖性蛋白激酶刺激表皮生长因子受体的表皮生长因子依赖性磷酸化。
DOI: --
发表时间: 1984
期刊: The Journal of biological chemistry
影响因子: --
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A-431 细胞的纯化表皮生长因子受体激酶对酪氨酸磷酸化的动力学。
DOI: --
发表时间: 1983
期刊: The Journal of biological chemistry
影响因子: --
作者:
Erneux,C;Cohen,S;Garbers,DL
通讯作者: Garbers,DL
DOI: --
发表时间: 1985
期刊: The Journal of biological chemistry
影响因子: --
作者:
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通讯作者: Brautigan,DL