Spatial regulation of signaling by the coordinated action of the protein tyrosine kinases MET and FER

doi:10.1016/j.cellsig.2018.06.006

	Spatial regulation of signaling by the coordinated action of the protein tyrosine kinases MET and FER
	Zhang, Jiali1 ; Wang, Zuo1 ; Zhang, Siwei 2,3; Chen, Yanxun 4; Xiong, Xuexue1 ; Li, Xiaojuan1 ; Tonks, Nicholas K.2; Fan, Gaofeng1,2
	2018-10
发表期刊	CELLULAR SIGNALLING (IF:4.4[JCR-2023],4.4[5-Year])
ISSN	0898-6568
卷号	50 页码:100-110
发表状态	已发表
DOI	10.1016/j.cellsig.2018.06.006
摘要	A critical aspect of understanding the regulation of signal transduction is not only to identify the protein-protein interactions that govern assembly of signaling pathways, but also to understand how those pathways are regulated in time and space. In this report, we have applied both gain-of-function and loss-of-function analyses to assess the role of the non-receptor protein tyrosine kinase FER in activation of the HGF Receptor protein tyrosine kinase MET. Overexpression of FER led to direct phosphorylation of several signaling sites in MET, including Tyr1349, but not the activation loop residues Tyr1234/5; in contrast, suppression of FER by RNAi revealed that phosphorylation of both a C-terminal signaling site (Tyr1349) and the activation loop (Tyr1234/5) were influenced by the function of this kinase. Adaptin beta, a component of the adaptor protein complex 2 (AP-2) that links clathrin to receptors in coated vesicles, was recruited to MET following FER-mediated phosphorylation. Furthermore, we provide evidence to support a role of FER in maintaining plasma membrane distribution of MET and thereby delaying protein-tyrosine phosphatase PTP1B-mediated inactivation of the receptor. Simultaneous up-regulation of FER and down-regulation of PTP1B observed in ovarian carcinoma-derived cell lines would be expected to contribute to persistent activation of HGF-MET signaling, suggesting that targeting of both FER and MET may be an effective strategy for therapeutic intervention in ovarian cancer.
关键词	FER MET PTP1B Endocytosis Ovarian cancer
收录类别	SCI ; SCIE
语种	英语
资助项目	Cold Spring Harbor Laboratory Cancer Centre Support Grant[CA45508]
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000441493100010
出版者	ELSEVIER SCIENCE INC
WOS关键词	C-MET ; OVARIAN-CANCER ; PHOSPHATASE 1B ; GROWTH-FACTOR ; QUANTITATIVE PROTEOMICS ; RECEPTOR ; ENDOCYTOSIS ; INHIBITOR ; INVASION ; CELLS
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/27590
专题	生命科学与技术学院生命科学与技术学院_PI研究组_范高峰组生命科学与技术学院_硕士生
通讯作者	Tonks, Nicholas K.; Fan, Gaofeng
作者单位	1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 2.Cold Spring Harbor Lab, POB 100, Cold Spring Harbor, NY 11724 USA 3.SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA 4.Fujian Med Univ, Affiliated Hosp 1, Fuzhou 350005, Fujian, Peoples R China
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院
第一作者的第一单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Zhang, Jiali,Wang, Zuo,Zhang, Siwei,et al. Spatial regulation of signaling by the coordinated action of the protein tyrosine kinases MET and FER[J]. CELLULAR SIGNALLING,2018,50:100-110.
APA	Zhang, Jiali.,Wang, Zuo.,Zhang, Siwei.,Chen, Yanxun.,Xiong, Xuexue.,...&Fan, Gaofeng.(2018).Spatial regulation of signaling by the coordinated action of the protein tyrosine kinases MET and FER.CELLULAR SIGNALLING,50,100-110.
MLA	Zhang, Jiali,et al."Spatial regulation of signaling by the coordinated action of the protein tyrosine kinases MET and FER".CELLULAR SIGNALLING 50(2018):100-110.