Download MendeleyStructure of a pseudokinase-domain switch that controls oncogenic activation of Jak kinases.
Toms, A.V., Deshpande, A., McNally, R., Jeong, Y., Rogers, J.M., Kim, C.U., Gruner, S.M., Ficarro, S.B., Marto, J.A., Sattler, M., Griffin, J.D., Eck, M.J.(2013) Nat Struct Mol Biol 20: 1221-1223
- PubMed: 24013208
- DOI: https://doi.org/10.1038/nsmb.2673
- Primary Citation of Related Structures:
4L00, 4L01 - PubMed 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.
Organizational Affiliation:
1] Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
