Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Oct;20(10):1221-3.
doi: 10.1038/nsmb.2673. Epub 2013 Sep 8.

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

Angela V Toms  1 , Anagha Deshpande, Randall McNally, Youngjee Jeong, Julia M Rogers, Chae Un Kim, Sol M Gruner, Scott B Ficarro, Jarrod A Marto, Martin Sattler, James D Griffin, Michael J Eck
Affiliations

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

Angela V Toms et al. Nat Struct Mol Biol. 2013 Oct.

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Figure 2
Figure 2
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Baker SJ, Rane SG, Reddy EP. Hematopoietic cytokine receptor signaling. Oncogene. 2007;26:6724–37. - PubMed
    1. Ghoreschi K, Laurence A, O'Shea JJ. Janus kinases in immune cell signaling. Immunol Rev. 2009;228:273–87. - PMC - PubMed
    1. Saharinen P, Takaluoma K, Silvennoinen O. Regulation of the Jak2 tyrosine kinase by its pseudokinase domain. Mol Cell Biol. 2000;20:3387–95. - PMC - PubMed
    1. Ihle JN, Gilliland DG. Jak2: normal function and role in hematopoietic disorders. Curr Opin Genet Dev. 2007;17:8–14. - PubMed
    1. Haan C, Behrmann I, Haan S. Perspectives for the use of structural information and chemical genetics to develop inhibitors of Janus kinases. J Cell Mol Med. 2010;14:504–27. - PMC - PubMed

Publication types