The JAK-STAT pathway: impact on human disease and therapeutic intervention

Annu Rev Med. 2015;66:311-28. doi: 10.1146/annurev-med-051113-024537.


The Janus kinase (JAK)-signal transducer of activators of transcription (STAT) pathway is now recognized as an evolutionarily conserved signaling pathway employed by diverse cytokines, interferons, growth factors, and related molecules. This pathway provides an elegant and remarkably straightforward mechanism whereby extracellular factors control gene expression. It thus serves as a fundamental paradigm for how cells sense environmental cues and interpret these signals to regulate cell growth and differentiation. Genetic mutations and polymorphisms are functionally relevant to a variety of human diseases, especially cancer and immune-related conditions. The clinical relevance of the pathway has been confirmed by the emergence of a new class of therapeutics that targets JAKs.

Keywords: autoimmunity; cancer; cytokine; immunodeficiency; kinase inhibitors.

Publication types

  • Review

MeSH terms

  • Gene Expression Regulation
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunologic Deficiency Syndromes / genetics*
  • Janus Kinases / genetics*
  • Janus Kinases / metabolism
  • Neoplasms / genetics*
  • STAT Transcription Factors / genetics*
  • STAT Transcription Factors / metabolism
  • Signal Transduction


  • STAT Transcription Factors
  • Janus Kinases