Journal article

Enzymatic Characterization of Wild-Type and Mutant Janus Kinase 1

Nicholas PD Liau, Artem Laktyushin, Rhiannon Morris, Jarrod J Sandow, Nicos A Nicola, Nadia J Kershaw, Jeffrey J Babon

CANCERS | MDPI | Published : 2019

Abstract

Janus kinases (JAKs) are found constitutively associated with cytokine receptors and are present in an inactive state prior to cytokine exposure. Activating mutations of JAKs are causative for a number of leukemias, lymphomas, and myeloproliferative diseases. In particular, the JAK2V617F mutant is found in most human cases of polycythemia vera, a disease characterized by over-production of erythrocytes. The V617F mutation is found in the pseudokinase domain of JAK2 and it leads to cytokine-independent activation of the kinase, as does the orthologous mutation in other JAK-family members. The mechanism whereby this mutation hyperactivates these kinases is not well understood, primarily due to..

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