FGF-receptor substrate 2 functions as a molecular sensor integrating external regulatory signals into the FGF pathway

	FGF-receptor substrate 2 functions as a molecular sensor integrating external regulatory signals into the FGF pathway
	Zhou, WC; Feng, XJ; Wu, YJ; Benge, J; Zhang, Z; Chen, ZJ
刊名	CELL RESEARCH
	2009
卷号	19 期号:10 页码:1165-1177
关键词	fibroblast growth factor (FGF) epithelial growth factor (EGF) crosstalk threonine phosphorylation co-stimulation
通讯作者	Chen, ZJ (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol,Grad Univ, 320 Yueyang Rd, Shanghai 200031, Peoples R China.,zjchen@sibs.ac.cn
英文摘要	Fibroblast growth factor (FGF) receptor substrate 2 alpha (FRS2 alpha) is the main mediator of signaling in the FGF pathway. Recent studies have shown that mitogen-activated protein kinase ( MAPK) phosphorylates serine and threonine residues in FRS2, negatively affecting FGF-induced tyrosine phosphorylation (PY) of FRS2. Several kinds of stimuli can induce serine/threonine phosphorylation (PS/T) of FRS2, indicating that FRS2 may be useful for studying crosstalk between growth factor signaling pathways. Here, we report that FGF-induced PY of FRS2 can be attenuated by EGF co-stimulation in PC12 cells; this inhibitory effect could be completely reversed by U0126, an inhibitor of MEK. We further identified the ERK1/2-binding motif in FRS2 and generated FRS2-3KL, a mutant lacking MAPK binding and PT upon FGF and/or EGF stimulation. Unlike wild-type (WT) FRS2, FGF-induced PY of FRS2-3KL could not be inhibited by EGF co-stimulation, and FRS2-3KL-expressing PC12 cells exhibited more differentiating potential than FRS2-WT-expressing cells in response to FGF treatment. These results suggest that PS/T of FRS2 mediated by the FRS2-MAPK negative regulatory loop may function as a molecular switch integrating negative regulatory signals from other pathways into FGFR-generated signal transduction.
学科主题	Cell Biology
类目[WOS]	Cell Biology
关键词[WOS]	FIBROBLAST-GROWTH-FACTOR ; DOCKING-PROTEIN FRS2-ALPHA ; PC12 CELL-DIFFERENTIATION ; TYROSINE KINASE-ACTIVITY ; MAP KINASE ; PHOSPHATIDYLINOSITOL 3-KINASE ; NEUROTROPHIC RECEPTORS ; 3T3-L1 ADIPOCYTES ; FRS2 ; ACTIVATION
收录类别	SCI
语种	英语
WOS记录号	WOS:000270527600005
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1248]
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	Zhou, WC,Feng, XJ,Wu, YJ,et al. FGF-receptor substrate 2 functions as a molecular sensor integrating external regulatory signals into the FGF pathway[J]. CELL RESEARCH,2009,19(10):1165-1177.
APA	Zhou, WC,Feng, XJ,Wu, YJ,Benge, J,Zhang, Z,&Chen, ZJ.(2009).FGF-receptor substrate 2 functions as a molecular sensor integrating external regulatory signals into the FGF pathway.CELL RESEARCH,19(10),1165-1177.
MLA	Zhou, WC,et al."FGF-receptor substrate 2 functions as a molecular sensor integrating external regulatory signals into the FGF pathway".CELL RESEARCH 19.10(2009):1165-1177.