TY  - JOUR
A1  - Reckel, Sina
A1  - Gehin, Charlotte
A1  - Tardivon, Delphine
A1  - Georgeon, Sandrine
A1  - Kükenshöner, Tim
A1  - Löhr, Frank
A1  - Koide, Akiko
A1  - Buchner, Lena
A1  - Panjkovich, Alejandro
A1  - Reynaud, Aline
A1  - Pinho, Sara
A1  - Gerig, Barbara
A1  - Svergun, Dmitri
A1  - Pojer, Florence
A1  - Güntert, Peter
A1  - Dötsch, Volker
A1  - Koide, Shohei
A1  - Gavin, Anne-Claude
A1  - Hantschel, Oliver
T1  - Structural and functional dissection of the DH and PH domains of oncogenic Bcr-Abl tyrosine kinase
T2  - Nature Communications
N2  - 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.
KW  - Kinases
KW  - SAXS
KW  - Solution-state NMR
KW  - X-ray crystallography
Y1  - 2017
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/45610
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-456101
SN  - 2041-1723
N1  - Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/. © The Author(s) 2017
VL  - 8
IS  - 1, Art. 2101
SP  - 1
EP  - 14
PB  - Nature Publishing Group UK
CY  - [London]
ER  -