Structure of a pseudokinase-domain switch that controls oncogenic activation of Jak kinases.
Publication Type:Journal Article
Source:Nat Struct Mol Biol, Volume 20, Issue 10, p.1221-3 (2013)
Keywords:Enzyme Activation, Humans, Janus Kinases, Models, Molecular, Oncogenes, Protein Conformation
<p>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. </p>