Molecular basis for pseudokinase-dependent autoinhibition of JAK2 tyrosine kinase

Yibing Shan,Kavitha Gnanasambandan,Daniela Ungureanu,Eric T Kim,Henrik Hammarén,Kazuo Yamashita,Olli Silvennoinen,David E Shaw,Stevan R Hubbard

NATURE STRUCTURAL & MOLECULAR BIOLOGY（2014）

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摘要

Cancer-associated mutations in the pseudokinase domain (JH2) of JAK2 lead to constitutive activation of its tandem kinase domain (JH1). Molecular dynamics simulations, supported by mutational analysis, provide a model for JH2-JH1 interactions that explains many of the JAK2-activating disease mutations.

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nature structural and molecular biology, science

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