The Janus kinases (Jaks)

Kunihiro Yamaoka, Pipsa Saharinen, Marko Pesu, Vance E T Holt, Olli Silvennoinen, John J. O'Shea

Research output: Contribution to journalArticle

329 Citations (Scopus)

Abstract

The Janus kinase (Jak) family is one of ten recognized families of non-receptor tyrosine kinases. Mammals have four members of this family, Jak1, Jak2, Jak3 and Tyrosine kinase 2 (Tyk2). Birds, fish and insects also have Jaks. Each protein has a kinase domain and a catalytically inactive pseudo-kinase domain, and they each bind cytokine receptors through amino-terminal FERM (Band-4.1, ezrin, radixin, moesin) domains. Upon binding of cytokines to their receptors, Jaks are activated and phosphorylate the receptors, creating docking sites for signaling molecules, especially members of the signal transducer and activator of transcription (Stat) family. Mutations of the Drosophila Jak (Hopscotch) have revealed developmental defects, and constitutive activation of Jaks in flies and humans is associated with leukemia-like syndromes. Through the generation of Jak-deficient cell lines and gene-targeted mice, the essential, nonredundant functions of Jaks in cytokine signaling have been established. Importantly, deficiency of Jak3 is the basis of human autosomal recessive severe combined immunodeficiency (SCID); accordingly, a selective Jak3 inhibitor has been developed, forming a new class of immunosuppressive drugs.

Original languageEnglish
Article number253
JournalGenome Biology
Volume5
Issue number12
DOIs
Publication statusPublished - 2004
Externally publishedYes

Fingerprint

non-specific protein-tyrosine kinase
Janus Kinases
phosphotransferases (kinases)
transducer
tyrosine
Janus Kinase 1
cytokines
Phosphotransferases
defect
TYK2 Kinase
inhibitor
mutation
severe combined immunodeficiency
drug
mammal
Cytokines
immunosuppressive agents
Severe Combined Immunodeficiency
insect
receptors

ASJC Scopus subject areas

  • Genetics
  • Cell Biology
  • Ecology, Evolution, Behavior and Systematics

Cite this

Yamaoka, K., Saharinen, P., Pesu, M., Holt, V. E. T., Silvennoinen, O., & O'Shea, J. J. (2004). The Janus kinases (Jaks). Genome Biology, 5(12), [253]. https://doi.org/10.1186/gb-2004-5-12-253

The Janus kinases (Jaks). / Yamaoka, Kunihiro; Saharinen, Pipsa; Pesu, Marko; Holt, Vance E T; Silvennoinen, Olli; O'Shea, John J.

In: Genome Biology, Vol. 5, No. 12, 253, 2004.

Research output: Contribution to journalArticle

Yamaoka, K, Saharinen, P, Pesu, M, Holt, VET, Silvennoinen, O & O'Shea, JJ 2004, 'The Janus kinases (Jaks)', Genome Biology, vol. 5, no. 12, 253. https://doi.org/10.1186/gb-2004-5-12-253
Yamaoka K, Saharinen P, Pesu M, Holt VET, Silvennoinen O, O'Shea JJ. The Janus kinases (Jaks). Genome Biology. 2004;5(12). 253. https://doi.org/10.1186/gb-2004-5-12-253
Yamaoka, Kunihiro ; Saharinen, Pipsa ; Pesu, Marko ; Holt, Vance E T ; Silvennoinen, Olli ; O'Shea, John J. / The Janus kinases (Jaks). In: Genome Biology. 2004 ; Vol. 5, No. 12.
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