ShanghaiTech University Knowledge Management System
Regulation of EGFR nanocluster formation by ionic protein-lipid interaction | |
2014 | |
发表期刊 | CELL RESEARCH |
ISSN | 1001-0602 |
EISSN | 1748-7838 |
卷号 | 24期号:8页码:959-976 |
发表状态 | 已发表 |
DOI | 10.1038/cr.2014.89 |
摘要 | The abnormal activation of epidermal growth factor receptor (EGFR) is strongly associated with a variety of human cancers but the underlying molecular mechanism is not fully understood. By using direct stochastic optical reconstruction microscopy (dSTORM), we find that EGFR proteins form nanoclusters in the cell membrane of both normal lung epithelial cells and lung cancer cells, but the number and size of clusters significantly increase in lung cancer cells. The formation of EGFR clusters is mediated by the ionic interaction between the anionic lipid phosphatidylinositol- 4,5-bisphosphate (PIP2) in the plasma membrane and the juxtamembrane (JM) region of EGFR. Disruption of EGFR clustering by PIP2 depletion or JM region mutation impairs EGFR activation and downstream signaling. Furthermore, JM region mutation in constitutively active EGFR mutant attenuates its capability of cell transformation. Collectively, our findings highlight the key roles of anionic phospholipids in EGFR signaling and function, and reveal a novel mechanism to explain the aberrant activation of EGFR in cancers. |
关键词 | EGFR clustering PIP2 the juxtamembrane region ionic interaction |
URL | 查看原文 |
收录类别 | SCI |
WOS研究方向 | Cell Biology |
WOS类目 | Cell Biology |
WOS记录号 | WOS:000343133700010 |
出版者 | INST BIOCHEMISTRY & CELL BIOLOGY |
WOS关键词 | GROWTH-FACTOR RECEPTOR ; OPTICAL RECONSTRUCTION MICROSCOPY ; PLASMA-MEMBRANE ; LUNG-CANCER ; LIVING CELLS ; DIFFRACTION-LIMIT ; KINASE DOMAIN ; SH3 DOMAIN ; EP-CAM ; ACTIVATION |
原始文献类型 | Article |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/119800 |
专题 | 个人在本单位外知识产出 |
通讯作者 | Xu, Chenqi; Ji, Hongbin; Wang, Hongda |
作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China 2.Chinese Acad Sci, Changchun Inst Appl Chem, State Key Lab Electroanalyt Chem, Changchun 130022, Jilin, Peoples R China 3.Chinese Acad Sci, Natl Ctr Prot Sci Shanghai, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci,State Key Lab Mol Biol, Shanghai 200031, Peoples R China 4.Jilin Univ, Hosp 2, Dept Thorac Surg, Changchun 130041, Jilin, Peoples R China 5.NE Normal Univ, Sch Comp Sci & Informat Technol, Changchun 130117, Jilin, Peoples R China 6.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 7.Second Mil Med Univ, Changhai Hosp, Dept Oncol, Shanghai 200433, Peoples R China |
推荐引用方式 GB/T 7714 | Wang, Ye,Gao, Jing,Guo, Xingdong,et al. Regulation of EGFR nanocluster formation by ionic protein-lipid interaction[J]. CELL RESEARCH,2014,24(8):959-976. |
APA | Wang, Ye.,Gao, Jing.,Guo, Xingdong.,Tong, Ti.,Shi, Xiaoshan.,...&Wang, Hongda.(2014).Regulation of EGFR nanocluster formation by ionic protein-lipid interaction.CELL RESEARCH,24(8),959-976. |
MLA | Wang, Ye,et al."Regulation of EGFR nanocluster formation by ionic protein-lipid interaction".CELL RESEARCH 24.8(2014):959-976. |
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