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

Publication Type:

Journal Article

Authors:

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

Source:

Nat Struct Mol Biol, Volume 20, Issue 10, p.1221-3 (2013)

Keywords:

Enzyme Activation, Humans, Janus Kinases, Models, Molecular, Oncogenes, Protein Conformation

Abstract:

<p>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. </p>

PDB: 
4L01
Detector: 
Q315
Beamline: 
24-ID-C