Jak-STAT Pathways and Transcriptional Activation in Response to IFNs and Other Extracellular Signaling Proteins

• Published in: Science (American Association for the Advancement of Science) 1994-06, Vol.264 (5164), p.1415-1421
• Main Authors: Darnell, James E., Kerr, Ian M., Stark, George R.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Biological and medical sciences; Cell Line; Cell lines; Cells; Cellular signal transduction; Complementary DNA; DNA; DNA-Binding Proteins - metabolism; Family members; Fundamental and applied biological sciences. Psychology; Genes; Genetic Complementation Test; Genetic transcription; Humans; Interferon; Interferon-alpha - pharmacology; Interferon-gamma - pharmacology; Interferon-Stimulated Gene Factor 3; Interferon-Stimulated Gene Factor 3, gamma Subunit; Ligands; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Mutation; Phosphorylation; Protein-Tyrosine Kinases - metabolism; Receptors; Regulatory Sequences, Nucleic Acid; Signal Transduction; Somatic cells; Transcription (Genetics); Transcription Factors - metabolism; Transcription. Transcription factor. Splicing. Rna processing; Transcriptional Activation
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.8197455

Through the study of transcriptional activation in response to interferon α (IFN-α) and interferon γ (IFN-γ), a previously unrecognized direct signal transduction pathway to the nucleus has been uncovered: IFN-receptor interaction at the cell surface leads to the activation of kinases of the Jak family that then phosphorylate substrate proteins called STATs (signal transducers and activators of transcription). The phosphorylated STAT proteins move to the nucleus, bind specific DNA elements, and direct transcription. Recognition of the molecules involved in the IFN-α and IFN-γ pathway has led to discoveries that a number of STAT family members exist and that other polypeptide ligands also use the Jak-STAT molecules in signal transduction.