Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1126/science.aav7532 |
Topological control of cytokine receptor signaling induces differential effects in hematopoiesis | |
Mohan, Kritika1; Ueda, George2,3; Kim, Ah Ram4,5,6; Jude, Kevin M.7; Fallas, Jorge A.2,3; Guo, Yu8,9; Hafer, Maximillian10; Miao, Yi1; Saxton, Robert A.1,7; Piehler, Jacob10,11; Sankaran, Vijay G.4,5,6; Baker, David2,3,12; Garcia, K. Christopher1,7,13 | |
2019-05-24 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2019 |
卷号 | 364期号:6442页码:750-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Peoples R China; Germany |
英文摘要 | Although tunable signaling by G protein-coupled receptors can be exploited through medicinal chemistry, a comparable pharmacological approach has been lacking for the modulation of signaling through dimeric receptors, such as those for cytokines. We present a strategy to modulate cytokine receptor signaling output by use of a series of designed C2-symmetric cytokine mimetics, based on the designed ankyrin repeat protein (DARPin) scaffold, that can systematically control erythropoietin receptor (EpoR) dimerization orientation and distance between monomers. We sampled a range of EpoR geometries by varying intermonomer angle and distance, corroborated by several ligand-EpoRcomplex crystal structures. Across the range, we observed full, partial, and biased agonism as well as stage-selective effects on hematopoiesis. This surrogate ligand strategy opens access to pharmacological modulation of therapeutically important cytokine and growth factor receptor systems. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000469296000034 |
WOS关键词 | ANKYRIN REPEAT ; TRANSMEMBRANE DOMAIN ; STRUCTURE REFINEMENT ; GROWTH-HORMONE ; ERYTHROPOIETIN ; DIMERIZATION ; PROTEINS ; AGONIST ; ACTIVATION ; PLEIOTROPY |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/201482 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA; 2.Univ Washington, Dept Biochem, Seattle, WA 98195 USA; 3.Univ Washington, Inst Prot Design, Seattle, WA 98195 USA; 4.Harvard Med Sch, Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Div Hematol Oncol, Boston, MA 02115 USA; 5.Harvard Med Sch, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA; 6.Broad Inst MIT & Harvard, Cambridge, MA 02142 USA; 7.Stanford Univ, Howard Hughes Med Inst, Sch Med, Stanford, CA 94305 USA; 8.Nankai Univ, State Key Lab Med Chem Biol, Tianjin, Peoples R China; 9.Nankai Univ, Coll Pharm, Tianjin, Peoples R China; 10.Univ Osnabruck, Div Biophys, Dept Biol, D-49076 Osnabruck, Germany; 11.Univ Osnabruck, Ctr Cellular Nanoanalyt, D-49076 Osnabruck, Germany; 12.Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA; 13.Stanford Univ, Sch Med, Dept Struct Biol, Stanford, CA 94305 USA |
推荐引用方式 GB/T 7714 | Mohan, Kritika,Ueda, George,Kim, Ah Ram,et al. Topological control of cytokine receptor signaling induces differential effects in hematopoiesis[J]. SCIENCE,2019,364(6442):750-+. |
APA | Mohan, Kritika.,Ueda, George.,Kim, Ah Ram.,Jude, Kevin M..,Fallas, Jorge A..,...&Garcia, K. Christopher.(2019).Topological control of cytokine receptor signaling induces differential effects in hematopoiesis.SCIENCE,364(6442),750-+. |
MLA | Mohan, Kritika,et al."Topological control of cytokine receptor signaling induces differential effects in hematopoiesis".SCIENCE 364.6442(2019):750-+. |
条目包含的文件 | 条目无相关文件。 |
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。
修改评论