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首页> 外文期刊>Journal of Cellular Physiology >Human mammary epithelial cells rapidly exchange empty EGFR between surface and intracellular pools.
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Human mammary epithelial cells rapidly exchange empty EGFR between surface and intracellular pools.

机译:人类乳腺上皮细胞快速交换空的表皮生长因子受体之间的表面和胞内池。

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Binding of ligand to the epidermal growth factor receptor (EGFR) initiates a series of processes including activation of the intrinsic EGFR tyrosine kinase, receptor autophosphorylation, and the assembly of active signaling complexes at the plasma membrane. Concomitantly, receptor trafficking is initiated, and the receptor is ultimately delivered to the lysosome, where it is degraded. Virtually all studies on EGFR trafficking have used fibroblasts and transformed cells. Because EGFR exerts a potent effect on the physiology of epithelial cells, we examined the regulation of EGFR activity and trafficking in nontransformed human mammary epithelial cells (HMEC). We found that HMEC that displayed a luminal phenotype were largely unresponsive to EGF and maintained a majority of their EGFR at the cell surface. In contrast, HMEC with a basal phenotype were highly responsive to EGF and, at steady state in the absence of exogenous ligand, distributed empty EGFR into intracellular pools. Maintenance of the intracellular pools was a direct consequence of specific and rapid endocytosis of the empty EGFR. The trafficking pattern was EGFR specific, used coated pits, and did not require receptor tyrosine kinase activity. Such an mechanism redistributes EGFR signaling potential among different membrane domains and into vesicles with unique biochemical microenviroments. In addition, our data show that EGFR endocytosis can be regulated in the absence of ligand binding and receptor activation in a cell-type-specific manner.
机译:表皮生长因子结合的配体受体(EGFR)发起的一系列过程包括内在的表皮生长因子受体的激活酪氨酸激酶受体自身磷酸化,和活动信号复合物的组装等离子体膜。开始贩卖,受体最终运送到溶酶体,它在哪里退化。贩卖用成纤维细胞和转化细胞。上皮细胞的生理机能,我们检查了表皮生长因子受体调节活动和贩卖是非人类乳腺上皮细胞(HMEC)。腔的表型在很大程度上反应迟钝大多数他们的表皮生长因子受体在EGF和维护细胞表面。表型是高度响应EGF和,稳态在缺乏外源配体,分布式空的表皮生长因子受体在细胞内池。维护细胞内池是一个具体的和快速的直接结果空的表皮生长因子受体的内吞作用。具体模式是表皮生长因子受体、涂层使用坑和不需要受体酪氨酸激酶吗活动。信号可能在不同的膜域和成囊泡具有独特的生化microenviroments。表皮生长因子受体的内吞作用可以在没有监管配体和受体的激活cell-type-specific方式。

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