Regulation of EGFR nanocluster formation by ionic protein-lipid interaction

	Regulation of EGFR nanocluster formation by ionic protein-lipid interaction
	Wang, Y; Gao, J; Guo, XD; Tong, T; Shi, XS; Li, LY; Qi, M; Wang, YJ; Cai, MJ; Jiang, JG
刊名	CELL RESEARCH
	2014
卷号	24 期号:8 页码:959-976
关键词	EGFR clustering PIP2 the juxtamembrane region ionic interaction
通讯作者	Wang, HD (reprint author), Chinese Acad Sci, Changchun Inst Appl Chem, State Key Lab Electroanalyt Chem, Changchun 130022, Jilin, Peoples R China.,cqxu@sibcb.ac.cn ; hbji@sibcb.ac.cn ; hdwang@ciac.ac.cn
英文摘要	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.
学科主题	Cell Biology
类目[WOS]	Cell Biology
关键词[WOS]	GROWTH-FACTOR RECEPTOR ; OPTICAL RECONSTRUCTION MICROSCOPY ; PLASMA-MEMBRANE ; LUNG-CANCER ; LIVING CELLS ; DIFFRACTION-LIMIT ; KINASE DOMAIN ; SH3 DOMAIN ; EP-CAM ; ACTIVATION
收录类别	SCI
语种	英语
WOS记录号	WOS:000343133700010
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/212]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Wang, Y,Gao, J,Guo, XD,et al. Regulation of EGFR nanocluster formation by ionic protein-lipid interaction[J]. CELL RESEARCH,2014,24(8):959-976.
APA	Wang, Y.,Gao, J.,Guo, XD.,Tong, T.,Shi, XS.,...&Wang, HD.(2014).Regulation of EGFR nanocluster formation by ionic protein-lipid interaction.CELL RESEARCH,24(8),959-976.
MLA	Wang, Y,et al."Regulation of EGFR nanocluster formation by ionic protein-lipid interaction".CELL RESEARCH 24.8(2014):959-976.