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. 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

Angela V Toms  1 , Anagha Deshpande, Randall McNally, Youngjee Jeong, Julia M Rogers, Chae Un Kim, Sol M Gruner, Scott B Ficarro, Jarrod A Marto, Martin Sattler, James D Griffin, Michael J Eck
Affiliations

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

Angela V Toms et al. Nat Struct Mol Biol. 2013 Oct.

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.

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