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

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2013

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Toms, A. V., A. Deshpande, R. McNally, Y. Jeong, J. M. Rogers, C. U. Kim, S. M. Gruner, et al. 2013. “Structure of a pseudokinase domain switch that controls oncogenic activation of Jak kinases.” Nature structural & molecular biology 20 (10): 10.1038/nsmb.2673. doi:10.1038/nsmb.2673. http://dx.doi.org/10.1038/nsmb.2673.

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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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