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

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 enc...

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Detalles Bibliográficos
Autores principales: Toms, Angela V., Deshpande, Anagha, McNally, Randall, Jeong, Youngjee, Rogers, Julia M., Kim, Chae Un, Gruner, Sol M., Ficarro, Scott B., Marto, Jarrod A., Sattler, Martin, Griffin, James D., Eck, Michael J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863620/
https://www.ncbi.nlm.nih.gov/pubmed/24013208
http://dx.doi.org/10.1038/nsmb.2673
Descripción
Sumario: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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