title: Molecular insights into regulation of JAK2 in myeloproliferative neoplasms.
abstract: The critical role of Janus kinase-2 (JAK2) in regulation of myelopoiesis was established 2 decades ago, but identification of mutations in the pseudokinase domain of JAK2 in myeloproliferative neoplasms (MPNs) and in other hematologic malignancies highlighted the role of JAK2 in human disease. These findings have revolutionized the diagnostics of MPNs and led to development of novel JAK2 therapeutics. However, the molecular mechanisms by which mutations in the pseudokinase domain lead to hyperactivation of JAK2 and clinical disease have been unclear. Here, we describe recent advances in the molecular characterization of the JAK2 pseudokinase domain and how pathogenic mutations lead to constitutive activation of JAK2.
authors.affiliation: School of Medicine, University of Tampere, Tampere, Finland; Clinical Hematology, Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; and.
authors.forename: Olli
authors.initials: O
authors.lastname: Silvennoinen
authors.affiliation: Kimmel Center for Biology and Medicine at the Skirball Institute and Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY.
authors.forename: Stevan R
authors.initials: SR
authors.lastname: Hubbard
mesh_terms: D000818:Animals; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D019337:Hematologic Neoplasms / Q000235:genetics*; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D053614:Janus Kinase 2 / Q000737:chemistry / Q000235:genetics*; D008958:Models, Molecular; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics
chemical_list: C507924:JAK2 protein, human; D053614:Janus Kinase 2
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