Article
Uncoupling JAK2 V617F activation from cytokine-induced signalling by modulation of JH2 αC helix.
The Biochemical journal - 1 Jun 2016
Leroy Emilie, Dusa Alexandra, Colau Didier, Motamedi Amir, Cahu Xavier, Mouton Céline, Huang Lily J, Shiau Andrew K, Constantinescu Stefan N
Abstract excerpt
The mechanisms by which JAK2 is activated by the prevalent pseudokinase (JH2) V617F mutation in blood cancers remain elusive. Via structure-guided mutagenesis and transcriptional and functional assays, we identify a community of residues from the JH2 helix αC, SH2-JH2 linker and JH1 kinase domain that mediate V617F-induced activation. This circuit is broken by altering the charge of residues along the...
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