Cell type dependent endocytic internalization of ErbB2 with an artificial peptide ligand that binds to ErbB2
Cell type dependent endocytic internalization of ErbB2 with an artificial peptide ligand that binds to ErbB2
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DOI：
10.1016/j.cellbi.2008.03.012
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发表时间：
2008-07-01
影响因子：
3.9
通讯作者：
Seno, Masaharu
中科院分区：
文献类型：
--
作者：
Hashizume, Toshihiro;Fukuda, Takayuki;Seno, Masaharu
ErbB 2是表皮生长因子（erbB）受体家族的成员，在乳腺癌和卵巢癌中经常过表达。抗体和小分子抗酪氨酸激酶抑制剂已被开发用于过表达erbB 2的癌症的靶向治疗。由配体诱导的erbB 2的内化和下调对于有效的治疗效果可能是重要的。然而，配体依赖性erbB 2内化尚未得到很好的表征。在这里，我们研究了在SKBr 3和SKOv 3细胞中erbB 2的内化，这两种细胞都过表达erbB 2，使用EC-1肽融合到eGFP（EC-eGFP），其特异性结合erbB 2。当细胞用EC-eGFP处理时，ErbB 2在SKOv 3细胞中内化。内体erbB 2的积累是EC-eGFP依赖性的，其与转铁蛋白共定位，这意味着通过网格蛋白包被的凹坑进行内吞作用。相反，在SKBr 3细胞中未观察到erbB 2的内化。因此，提出了两种不同的机制，这是细胞类型依赖于erbB 2的内化。(C)2008年国际细胞生物学联合会。由爱思唯尔有限公司出版。保留所有权利。
ErbB2, which is a member of the epidermal growth factor (erbB) receptor family, is frequently overexpressed in breast and ovarian cancers. Antibody and small molecule anti-tyrosine kinase inhibitors have been developed for targeted therapies for cancers overexpressing erbB2. Internalization and downregulation of erbB2, which is induced by a ligand, may be important for efficacious therapeutic effects. However, ligand-dependent erbB2 internalization has not been well characterized. Here we investigated the internalization of erbB2 in SKBr3 and SKOv3 cells, both overexpressing erbB2, using an EC-1 peptide fused to eGFP (EC-eGFP), which specifically binds to erbB2. ErbB2 was internalized in SKOv3 cells when the cells were treated with EC-eGFP. The accumulation of endosomal erbB2 was EC-eGFP dependent, which colocalized with transferrin implying endocytosis via clathrin-coated pits. In contrast, internalization of erbB2 was not observed in SKBr3 cells. As a result, two different mechanisms, which are cell type dependent for the internalization of erbB2, are proposed. (C) 2008 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.