JAKs in pathology: role of Janus kinases in hematopoietic malignancies and immunodeficiencies

Semin Cell Dev Biol. 2008 Aug;19(4):385-93. doi: 10.1016/j.semcdb.2008.07.002. Epub 2008 Jul 17.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Enzyme Activation
  • Hematologic Neoplasms / metabolism*
  • Humans
  • Immunologic Deficiency Syndromes / metabolism*
  • Isoenzymes / metabolism*
  • Janus Kinases / chemistry
  • Janus Kinases / genetics
  • Janus Kinases / metabolism*
  • Mutation
  • Receptors, Cytokine / chemistry
  • Receptors, Cytokine / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction / physiology*


  • Isoenzymes
  • Receptors, Cytokine
  • Recombinant Fusion Proteins
  • Janus Kinases