(2013) Toms, Angela V.; Deshpande, Anagha; McNally, Randall; Jeong, Youngjee; Rogers, Julia; Kim, Chae Un; Gruner, Sol M.; Ficarro, Scott; Marto, Jarrod; Sattler, Martin; Griffin, James; Eck, Michael
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.
