Schnurri-3 regulates ERK downstream of WNT signaling in osteoblasts

	Schnurri-3 regulates ERK downstream of WNT signaling in osteoblasts
	Shim, JH; Greenblatt, MB; Zou, WG; Huang, ZW; Wein, MN; Brady, N; Hu, D; Charron, J; Brodkin, HR; Petsko, GA
刊名	JOURNAL OF CLINICAL INVESTIGATION
	2013
卷号	123 期号:9 页码:4010-4022
通讯作者	Shim, JH (reprint author), Weill Cornell Med Coll, 1300 York Ave E907, New York, NY 10065 USA.,jas2060@med.cornell.edu ; lglimche@med.cornell.edu
英文摘要	Mice deficient in Schnurri-3 (SHN3; also known as HIVEP3) display increased bone formation, but harnessing this observation for therapeutic benefit requires an improved understanding of how SHN3 functions in osteoblasts. Here we identified SHN3 as a dampener of ERK activity that functions in part downstream of WNT signaling in osteoblasts. A D-domain motif within SHN3 mediated the interaction with and inhibition of ERK activity and osteoblast differentiation, and knockin of a mutation in Shn3 that abolishes this interaction resulted in aberrant ERK activation and consequent osteoblast hyperactivity in vivo. Additionally, in vivo genetic interaction studies demonstrated that crossing to Lrp5(-/-) mice partially rescued the osteosclerotic phenotype of Shn3(-/-) mice; mechanistically, this corresponded to the ability of SHN3 to inhibit ERK-mediated suppression of GSK3 beta. Inducible knockdown of Shn3 in adult mice resulted in a high-bone mass phenotype, providing evidence that transient blockade of these pathways in adults holds promise as a therapy for osteoporosis.
学科主题	Research & Experimental Medicine
类目[WOS]	Medicine, Research & Experimental
关键词[WOS]	WNT/BETA-CATENIN ; SKELETAL DEVELOPMENT ; KINASE ACTIVATION ; BETA-CATENIN ; MAP KINASES ; DIFFERENTIATION ; GROWTH ; MICE ; SUBSTRATE ; MOTIF
收录类别	SCI
语种	英语
WOS记录号	WOS:000324562600042
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/425]
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	Shim, JH,Greenblatt, MB,Zou, WG,et al. Schnurri-3 regulates ERK downstream of WNT signaling in osteoblasts[J]. JOURNAL OF CLINICAL INVESTIGATION,2013,123(9):4010-4022.
APA	Shim, JH.,Greenblatt, MB.,Zou, WG.,Huang, ZW.,Wein, MN.,...&Jones, DC.(2013).Schnurri-3 regulates ERK downstream of WNT signaling in osteoblasts.JOURNAL OF CLINICAL INVESTIGATION,123(9),4010-4022.
MLA	Shim, JH,et al."Schnurri-3 regulates ERK downstream of WNT signaling in osteoblasts".JOURNAL OF CLINICAL INVESTIGATION 123.9(2013):4010-4022.