Signal transduction and activation of gene transcription by interferons

Advances in the field of interferon research have identified a signal transduction pathway that initiates at a cell surface receptor and culminates at target genes in the nucleus. The binding of interferon to a transmembrane receptor stimulates the concomitant activation of tyrosine kinases of the Janus kinase (JAK) family. Subsequently, latent cytoplasmic transcription factors are activated by tyrosine phosphorylation and function as signal transducers and activators of transcription (STATs). The STATs form homomeric or heteromeric protein complexes that translocate to the nucleus to bind to specific DNA sequences in the promoters of stimulated genes. The discovery of this regulated pathway in the interferon system served as a paradigm for receptor to nucleus signal transmission by a variety of cytokines.