Schnurri-3 regulates ERK downstream of WNT signaling in osteoblasts
文献类型：期刊论文
| 作者 | 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
 |
| 出版日期 | 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 |
| 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. |
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