Structure of a pseudokinase-domain switch that controls oncogenic activation of Jak kinases.
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ABSTRACT:
SUBMITTER: Toms AV
PROVIDER: S-EPMC3863620 | biostudies-literature | 2013 Oct
REPOSITORIES: biostudies-literature
Publications
Structure of a pseudokinase-domain switch that controls oncogenic activation of Jak kinases.
Toms Angela V AV Deshpande Anagha A McNally Randall R Jeong Youngjee Y Rogers Julia M JM Kim Chae Un CU Gruner Sol M SM Ficarro Scott B SB Marto Jarrod A JA Sattler Martin M Griffin James D JD Eck Michael J MJ
Nature structural & molecular biology 20130908 10
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. ...[more]
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