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Nat Struct Mol Biol. 2013 Oct;20(10):1221-3. doi: 10.1038/nsmb.2673. Epub 2013 Sep 8.

Structure of a pseudokinase-domain switch that controls oncogenic activation of Jak kinases.

Author information

1
1] Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.

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.

PMID:
24013208
PMCID:
PMC3863620
DOI:
10.1038/nsmb.2673
[Indexed for MEDLINE]
Free PMC Article

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