Structural and functional dissection of the DH and PH domains of oncogenic Bcr-Abl tyrosine kinase

doi:10.1038/s41467-018-05133-4

GSTDTAP > 资源环境科学

DOI	10.1038/s41467-018-05133-4
	Structural and functional dissection of the DH and PH domains of oncogenic Bcr-Abl tyrosine kinase
	Reckel, Sina 1; Gehin, Charlotte 2; Tardivon, Delphine 1; Georgeon, Sandrine 1; Kukenshoner, Tim 1; Loehr, Frank 3; Koide, Akiko 4,5,6; Buchner, Lena 3; Panjkovich, Alejandro 7; Reynaud, Aline 8; Pinho, Sara 1; Gerig, Barbara 1; Svergun, Dmitri 7; Pojer, Florence 8; Guentert, Peter 3,9,10; Doetsch, Volker 3; Koide, Shohei 4,5,6; Gavin, Anne-Claude 2; Hantschel, Oliver 1
	2017-12-13
发表期刊	NATURE COMMUNICATIONS
ISSN	2041-1723
出版年	2017
卷号	8
文章类型	Article
语种	英语
国家	Switzerland; Germany; USA; Japan
英文摘要	The two isoforms of the Bcr-Abl tyrosine kinase, p210 and p190, are associated with different leukemias and have a dramatically different signaling network, despite similar kinase activity. To provide a molecular rationale for these observations, we study the Dbl-homology (DH) and Pleckstrin-homology (PH) domains of Bcr-Abl p210, which constitute the only structural differences to p190. Here we report high-resolution structures of the DH and PH domains and characterize conformations of the DH-PH unit in solution. Our structural and functional analyses show no evidence that the DH domain acts as a guanine nucleotide exchange factor, whereas the PH domain binds to various phosphatidylinositol-phosphates. PH-domain mutants alter subcellular localization and result in decreased interactions with p210-selective interaction partners. Hence, the PH domain, but not the DH domain, plays an important role in the formation of the differential p210 and p190 Bcr-Abl signaling networks.
领域	资源环境
收录类别	SCI-E
WOS记录号	WOS:000417884500007
WOS关键词	SMALL-ANGLE SCATTERING ; RHO-FAMILY GTPASES ; X-RAY-SCATTERING ; C-ABL ; CRYSTAL-STRUCTURE ; SH2 DOMAIN ; BIOLOGICAL MACROMOLECULES ; SELECTIVE-ACTIVATION ; PROTEINS ; COMPLEX
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
URL	查看原文
引用统计	被引频次：31[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/203890
专题	资源环境科学
作者单位	1.Ecole Polytech Fed Lausanne, Sch Life Sci, Swiss Inst Expt Canc Res ISREC, CH-1015 Lausanne, Switzerland; 2.European Mol Biol Lab, Struct & Computat Biol Unit, D-69117 Heidelberg, Germany; 3.Goethe Univ Frankfurt, Inst Biophys Chem, D-60438 Frankfurt, Germany; 4.NYU, Langone Med Ctr, Laura & Isaac Perlmutter Canc Ctr, New York, NY 10016 USA; 5.NYU, Sch Med, Dept Med, New York, NY 10016 USA; 6.NYU, Sch Med, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA; 7.European Mol Biol Lab, Hamburg Outstn, D-22607 Hamburg, Germany; 8.Ecole Polytech Fed Lausanne, Sch Life Sci, Prot Crystallog Core Facil, CH-1015 Lausanne, Switzerland; 9.Swiss Fed Inst Technol, Phys Chem Lab, CH-8093 Zurich, Switzerland; 10.Tokyo Metropolitan Univ, Grad Sch Sci, Tokyo 1920397, Japan
推荐引用方式 GB/T 7714	Reckel, Sina,Gehin, Charlotte,Tardivon, Delphine,et al. Structural and functional dissection of the DH and PH domains of oncogenic Bcr-Abl tyrosine kinase[J]. NATURE COMMUNICATIONS,2017,8.
APA	Reckel, Sina.,Gehin, Charlotte.,Tardivon, Delphine.,Georgeon, Sandrine.,Kukenshoner, Tim.,...&Hantschel, Oliver.(2017).Structural and functional dissection of the DH and PH domains of oncogenic Bcr-Abl tyrosine kinase.NATURE COMMUNICATIONS,8.
MLA	Reckel, Sina,et al."Structural and functional dissection of the DH and PH domains of oncogenic Bcr-Abl tyrosine kinase".NATURE COMMUNICATIONS 8(2017).