Suppr超能文献

表皮生长因子与A431细胞的异常结合是由于高受体密度和可饱和内吞系统的作用。

Anomalous binding of epidermal growth factor to A431 cells is due to the effect of high receptor densities and a saturable endocytic system.

作者信息

Wiley H S

机构信息

Department of Pathology, University of Utah, Salt Lake City 84132.

出版信息

J Cell Biol. 1988 Aug;107(2):801-10. doi: 10.1083/jcb.107.2.801.

Abstract

This study was conducted to determine how extraordinarily high numbers of epidermal growth factor receptors (EGF-R) affected the binding and internalization of EGF in the transformed cell line A431. I found that at low EGF concentrations, the kinetics of binding behaved as a nonsaturable, first-order process showing no evidence of multiple-affinity classes of receptors. However, EGF dissociation rates were strongly dependent on the degree of receptor occupancy in both intact cells and isolated membranes. This occupancy-dependent dissociation appears to be due to diffusion-limited binding. EGF-induced receptor internalization was rapid and first order when the absolute number of occupied receptors was below 4 x 10(3) min-1. However, at higher occupancies the specific internalization rate progressively declined to a final limiting value of 20% normal. The saturation of EGF-R endocytosis was specific since internalization of transferrin receptors was not affected by high concentrations of either transferrin or EGF. Saturation of EGF-R endocytosis probably involves a specific component of the endocytic pathway since fluid phase endocytosis increased coordinately with EGF-R occupancy. I conclude that there are several aspects of EGF-R dynamics on A431 cells are neither similar to the behavior of EGF-R in other cell types nor similar to the reported behavior of other hormone receptors. Although A431 cells have an extraordinary number of EGF-R, they do not seem to have corresponding levels of at least two other crucial cell surface components: one that mediates EGF-induced rapid receptor internalization and one that attenuates EGF-induced membrane responses. These factors, in addition to the presence of diffusion-limited binding at low EGF concentrations, are probably responsible for the appearance of multiple-affinity classes of receptors in this cell type.

摘要

本研究旨在确定表皮生长因子受体(EGF-R)数量极高时如何影响转化细胞系A431中EGF的结合和内化。我发现,在低EGF浓度下,结合动力学表现为非饱和的一级过程,未显示出受体存在多亲和力类别。然而,EGF解离速率在完整细胞和分离膜中均强烈依赖于受体占有率。这种占有率依赖性解离似乎是由于扩散限制结合所致。当被占据受体的绝对数量低于4×10³ 分钟⁻¹时,EGF诱导的受体内化迅速且呈一级反应。然而,在更高的占有率下,特定内化速率逐渐下降至正常水平的最终极限值20%。EGF-R内吞作用的饱和是特异性的,因为转铁蛋白受体的内化不受高浓度转铁蛋白或EGF的影响。EGF-R内吞作用的饱和可能涉及内吞途径的特定成分,因为液相内吞作用与EGF-R占有率协同增加。我得出结论,A431细胞上EGF-R动力学的几个方面既不同于其他细胞类型中EGF-R的行为,也不同于其他激素受体的报道行为。尽管A431细胞具有大量的EGF-R,但它们似乎没有至少另外两种关键细胞表面成分的相应水平:一种介导EGF诱导的快速受体内化,另一种减弱EGF诱导的膜反应。除了在低EGF浓度下存在扩散限制结合外,这些因素可能是该细胞类型中出现受体多亲和力类别的原因。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验