Signal transduction by epidermal growth factor occurs through the subclass of high affinity receptors.
Signal transduction by epidermal growth factor occurs through the subclass of high affinity receptors.
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DOI：
10.1083/jcb.109.5.2495
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发表时间：
1989-11
期刊：
影响因子：
--
通讯作者：
de Laat SW
中科院分区：
文献类型：
--
作者：
Defize LH;Boonstra J;Meisenhelder J;Kruijer W;Tertoolen LG;Tilly BC;Hunter T;van Bergen en Henegouwen PM;Moolenaar WH;de Laat SW
根据表皮生长因子结合研究，许多细胞类型表现出两类表皮生长因子受体，即主要的低亲和力的EGFR和次要的高亲和力的EGFR。我们用抗EGFR mAb2E9研究了它们在EGF在人A431癌细胞中诱导的级联反应中各自的作用。这种抗体特异性地阻断EGF与低亲和力EGFR的结合，而不激活完整细胞中的受体，从而使我们能够研究独占EGF与高亲和力EGFR结合的效果。我们发现，mAb2E9阻断低亲和力的EGFR对EGF激活受体蛋白酪氨酸激酶几乎没有影响，提示EGFR的激活仅通过高亲和力的EGFR亚类(5-10%)发生。此外，我们提供了高亲和力EGFR以单体和二聚体形式存在的证据，并且高亲和力EGFR对低亲和力EGFR的交叉磷酸化可能发生在两种受体类型的二聚体中。我们证明，在mAb2E9存在下，细胞对EGF的早期反应也不会受到损害：(A)肌醇磷酸产生，(B)细胞内钙离子释放，(C)细胞内pH升高，(D)EGF在苏氨酸残基654上的磷酸化，(E)诱导c-fos基因表达，以及(F)细胞形态改变。作为可能的非特异性副作用，我们观察到在mAb2E9存在的情况下，EGF诱导的钙内流和液相吞饮作用在A431细胞中被抑制。因此，我们得出结论，EGFR信号转导通路的激活完全可以通过EGF与高亲和力EGFR亚类的排他性结合而发生。
Many cell types display two classes of epidermal growth factor receptor (EGFR) as judged from EGF binding studies; i.e., a major class of low affinity EGFR and a minor class of high affinity EGFR. We have studied their respective contribution to the cascade of events elicited by EGF in human A431 carcinoma cells, using anti-EGFR mAb 2E9. This antibody specifically blocks EGF binding to low affinity EGFR, without activating receptors in intact cells, and thus enables us to study the effects of exclusive EGF binding to high affinity EGFR. We show that blocking of low affinity EGFR by mAb 2E9 has almost no effect on the activation of the receptor protein-tyrosine kinase by EGF, suggesting that EGFR kinase activation occurs exclusively through the subclass of high affinity EGFR (5-10%). In addition, we provide evidence that high affinity EGFR exists both in monomeric and dimeric forms, and that cross-phosphorylation of low affinity EGFR by high affinity EGFR may take place in dimers of both receptor types. We demonstrate that the following early cellular response to EGF are also unimpaired in the presence of mAb 2E9: (a) inositol phosphate production, (b) release of Ca2+ from intracellular stores, (c) rise in intracellular pH, (d) phosphorylation of EGF on threonine residue 654, (e) induction of c-fos gene expression, and (f) alteration in cell morphology. As possible nonspecific side effects, we observed that the EGF induced Ca2+ influx and fluid-phase pinocytosis were inhibited in A431 cells in the presence of mAb 2E9. We conclude, therefore, that the activation of the EGFR signal transduction cascade can occur completely through exclusive binding of EGF to the subclass of high affinity EGFR.
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缺乏血型A抗原显示的A431细胞变体增加了高亲和力表皮生长因子受体数，蛋白质酪氨酸激酶活性和受体更新。
影响因子：
7.8
作者：
Defize, L H;Arndt-Jovin, D J;Jovin, T M;Boonstra, J;Meisenhelder, J;Hunter, T;de Hey, H T;de Laat, S W
通讯作者：
de Laat, S W
影响因子：
56.9
作者：
COUSSENS, L;YANGFENG, TL;ULLRICH, A
通讯作者：
ULLRICH, A
影响因子：
11.4
作者：
GREGORIOU, M;REES, AR
通讯作者：
REES, AR
影响因子：
2.9
作者：
FANGER, BO;AUSTIN, KS;CIDLOWSKI, JA
通讯作者：
CIDLOWSKI, JA
影响因子：
64.8
作者：
CHEN, WS;LAZAR, CS;ROSENFELD, MG
通讯作者：
ROSENFELD, MG