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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme Activation
  • Humans
  • Janus Kinases / chemistry
  • Janus Kinases / metabolism*
  • Models, Molecular
  • Oncogenes*
  • Protein Conformation


  • Janus Kinases