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.

SUBMITTER: Toms AV 

PROVIDER: S-EPMC3863620 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature