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Smoothened transduces Hedgehog signal by forming a complex with Evc/Evc2
文献类型：期刊论文
| 作者 | Yang CP1; Chen WL2; Chen YB[*]1,3; Jiang J[*]3 |
| 刊名 | CELL RESEARCH
 |
| 出版日期 | 2012 |
| 卷号 | 22期号:11页码:1593-1604 |
| 关键词 | Evc Evc2 Hedgehog Smo Gli |
| 通讯作者 | ybchen@mail.kiz.ac.cn ; jin.jiang@utsouthwestern.edu |
| 合作状况 | 其它 |
| 英文摘要 | Hedgehog (Hh) signaling plays pivotal roles in embryonic development and adult tissue homeostasis in species ranging from Drosophila to mammals. The Hh signal is transduced by Smoothened (Smo), a seven-transmembrane protein related to G protein coupled receptors. Despite a conserved mechanism by which Hh activates Smo in Drosophila and mammals, how mammalian Hh signal is transduced from Smo to the Gli transcription factors is poorly understood. Here, we provide evidence that two ciliary proteins, Evc and Evc2, the products of human disease genes responsible for the Ellis-van Creveld syndrome, act downstream of Smo to transduce the Hh signal. We found that loss of Evc/Evc2 does not affect Sonic Hedgehog-induced Smo phosphorylation and ciliary localization but impedes Hh pathway activation mediated by constitutively active forms of Smo. Evc/Evc2 are dispensable for the constitutive Gli activity in Sufu(-/-) cells, suggesting that Evc/Evc2 act upstream of Sufu to promote Gli activation. Furthermore, we demonstrated that Hh stimulates binding of Evc/Evc2 to Smo depending on phosphorylation of the Smo C-terminal intracellular tail and that the binding is abolished in Kif3a(-/-) cilium-deficient cells. We propose that Hh activates Smo by inducing its phosphorylation, which recruits Evc/Evc2 to activate Gli proteins by antagonizing Sufu in the primary cilia. |
| 收录类别 | SCI |
| 资助信息 | Y Chen was supported by grants from the National Natural Science Foundation of China (31271579), the National Key Basic Research Program of China (2013CB910900), and American Heart Association postdoctoral fellowship (10POST3640046). J Jiang was supported by grants from NIH (GM61269 and GM067045), Welch Foundation (I-1603) and CPRIT (RP100561). C Yang and Y Chen were both supported by Kunming Institute of Zoology startup fund and Chinese Acad- emy of Sciences. |
| 语种 | 英语 |
| WOS记录号 | WOS:000310789500012 |
| 公开日期 | 2013-04-10 |
| 源URL | [http://159.226.149.42:8088/handle/152453/7353]  |
| 专题 | 昆明动物研究所_肿瘤信号转导 昆明动物研究所_动物模型与人类重大疾病机理重点实验室 |
| 作者单位 | 1.Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kun- ming Institute of Zoology, Chinese Academy of Sciences, 32 Jiaochang Donglu, Kunming, Yunnan 650223, China 2.The Depart- ment of Breast Tumor of the 3rd Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650118, China 3.Department of Developmental Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA |
| 推荐引用方式 GB/T 7714 | Yang CP,Chen WL,Chen YB[*],et al. Smoothened transduces Hedgehog signal by forming a complex with Evc/Evc2[J]. CELL RESEARCH,2012,22(11):1593-1604. |
| APA | Yang CP,Chen WL,Chen YB[*],&Jiang J[*].(2012).Smoothened transduces Hedgehog signal by forming a complex with Evc/Evc2.CELL RESEARCH,22(11),1593-1604. |
| MLA | Yang CP,et al."Smoothened transduces Hedgehog signal by forming a complex with Evc/Evc2".CELL RESEARCH 22.11(2012):1593-1604. |
入库方式： OAI收割
来源：昆明动物研究所
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