UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK.
Traffic. 2012 Feb;13(2):329-37. doi: 10.1111/j.1600-0854.2011.01305.x. Epub 2011 Nov 22.
Progression of activated EGF receptor (EGFR) through the endocytic pathway regulates EGFR signaling. Here we show that a non-ubiquitinated EGFR mutant, unable to bind the endosomal-sorting complex required for transport (ESCRT) component, Hrs, is not efficiently targeted onto intraluminal vesicles (ILVs) of multivesicular endosomes/bodies (MVBs). Moreover, ubiquitination and ESCRT engagement of activated EGFR are required for EGF-stimulated ILV formation. Non-ubiquitinated EGFRs enter clathrin-coated tubules emanating from MVBs and show enhanced recycling to the plasma membrane, compared to wild-type EGFR.
激活的表皮生长因子受体 (EGFR) 通过内吞途径的进展调节 EGFR 信号转导。在这里,我们表明,一种不能与内体分选复合物必需蛋白 (ESCRT) 成分 Hrs 结合的非泛素化 EGFR 突变体不能有效地靶向多泡体/液泡 (MVB) 的腔内小泡 (ILVs)。此外,激活的 EGFR 的泛素化和 ESCRT 结合对于 EGF 刺激的 ILV 形成是必需的。与野生型 EGFR 相比,非泛素化的 EGFR 进入从 MVB 发出的网格蛋白包被小管,并显示出增强的向质膜的循环回收。