The JAK-STAT Pathway

  • Warren J. Leonard
Part of the Endocrine Updates book series (ENDO, volume 17)


The JAK-STAT pathway is one of the central signaling pathways used by interferons and type I cytokines. Janus family tyrosine kinases (JAK kinases) are cytoplasmic tyrosine kinases that associate with cytokine receptor chains. These kinases are activated by cytokine binding, and then can phosphorylate the receptors on tyrosine residues. This in turn allows the recruitment of signal transducer and activator of transcription (STAT) proteins via their SH2 domains to the phosphorylated receptor. The STAT proteins are then also phosphorylated on tyrosine residue(s) by the JAK kinases, which allows the dimerization and nuclear translocation of the STAT proteins. STAT proteins then bind to target DNA sequences, modulating gene expression of certain genes. Thus, STAT proteins are latent transcription factors: they initially exist in the cytosol, but translocate to the nucleus following cellular activation. Together with NF-kB, NF-AT, and SMADs, STATs represent one of four types of transcription factors that are rapidly translocated from cytosol to nucleus in a fashion that is dependent on phosphorylation/dephosphorylation events. This short chapter cannot comprehensively review all that is known of the JAK-STAT pathway. Therefore, the goal will be to overview the basic system and describe some of the features of JAK kinases and STAT proteins, focusing on in vivo data, when available, from various knockout models. Many recent reviews of the JAK/STAT pathway should be consulted for in-depth review of other areas. We will begin with a brief discussion of “cytokines”, as these are the molecules that initiate the activation of the JAK/STAT pathway.


Serine Phosphorylation Severe Combine Immune Deficiency Latent Transcription Factor Stat2 Knockout Mouse Cytokine Receptor Chain 
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Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Warren J. Leonard
    • 1
  1. 1.Laboratory of Molecular Immunology, National Heart, Lung, and Blood InstituteNational Institutes of HealthBethesdaUSA

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