title: JAKs in pathology: role of Janus kinases in hematopoietic malignancies and immunodeficiencies.
abstract: The four mammalian Janus kinase (JAK) family members, JAK1, JAK2, JAK3 and TYK2, are non-receptor protein tyrosine kinases (PTKs) that are crucial for cytokine receptor signaling in blood formation and immune responses. Mutations and translocations in the JAK genes leading to constitutively active JAK proteins are associated with a variety of hematopoietic malignancies, including the myeloproliferative disorders (JAK2), acute lymphoblastic leukemia (JAK2), acute myeloid leukemia (JAK2, JAK1), acute megakaryoblastic leukemia (JAK2, JAK3) and T-cell precursor acute lymphoblastic leukemia (JAK1). In contrast, loss-of-function mutations of JAK3 and TYK2 lead to immunodeficiency. The role of JAKs as therapeutic targets is starting to expand, as more insights into their structure and activation mechanisms become available.
authors.affiliation: Institut Gustave Roussy PR 1, 94805 Villejuif, France. verpre@igr.fr
authors.forename: William
authors.initials: W
authors.lastname: Vainchenker
authors.forename: Alexandra
authors.initials: A
authors.lastname: Dusa
authors.forename: Stefan N
authors.initials: SN
authors.lastname: Constantinescu
mesh_terms: D000818:Animals; D004789:Enzyme Activation; D019337:Hematologic Neoplasms / Q000378:metabolism*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D053612:Janus Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D018121:Receptors, Cytokine / Q000737:chemistry / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D007527:Isoenzymes; D018121:Receptors, Cytokine; D011993:Recombinant Fusion Proteins; D053612:Janus Kinases