Structure of a pseudokinase-domain switch that controls oncogenic activation of Jak kinases
Abstract
The V617F mutation in the Jak2 pseudokinase domain causes myeloproliferative neoplasms, and the equivalent mutation in Jak1 (V658F) is found in T-cell leukemias. Crystal structures of wild-type and V658F-mutant human Jak1 pseudokinase reveal a conformational switch that remodels a linker segment encoded by exon 12, which is also a site of mutations in Jak2. This switch is required for V617F-mediated Jak2 activation and possibly for physiologic Jak activation. © 2013 Nature America, Inc. All rights reserved.
Date Published
Journal
Nature Structural and Molecular Biology
Volume
20
Issue
10
Number of Pages
1221-1224,
URL
https://www.scopus.com/inward/record.uri?eid=2-s2.0-84885418884&doi=10.1038%2fnsmb.2673&partnerID=40&md5=584519fda7ae6d0d771506a6e44245d1
DOI
10.1038/nsmb.2673
Research Area
Group (Lab)
Sol M. Gruner Group
Funding Source
CA936132
GM008313
R01CA134660