Of JAKs, STATs, blind watchmakers, jeeps and trains

FEBS Letters

Kerr, Ian M.¹  Lillemeier, Björn F.³  Strobl, Birgit²  Costa-Pereira, Ana P.¹ 

[1] Cancer Research UK London Research Institute, Lincoln's Inn Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK;Institute of Animal Breeding and Genetics, Veterinärplatz 1, A-1210 Vienna, Austria;Howard Hughes Medical Institute, Beckman Center, B215, Stanford University School of Medicine, 279 Campus Drive, Stanford, CA 94305-5323, USA

关键词: Interferon-γ;    Interleukin-6;    Receptor chimeras;    Janus kinase/signal transducer and activator of transcription signalling;    Signal transducer and activator of transcription-1–green fluorescent protein;    JAK;    Janus kinase;    STAT;    signal transducer and activator of transcription;    IFN;    interferon;    IL-6;    interleukin-6;    OSM;    oncostatin M;    IFNGR;    interferon-γ receptor;    PI3-kinase;    phosphatidylinositol 3-kinase;    ERK;    extracellular signal-regulated kinase;    GFP;    green fluorescent protein;    MEFs;    mouse embryonic fibroblasts;    ISGs;    interferon-stimulated genes;    MHC;    major histocompatibility complex;   

DOI  :  10.1016/S0014-5793(03)00411-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling is essential but not sufficient for full responses to the interferons (IFNs), most cytokines and some growth factors. The IFN-γ and interleukin-6 (IL-6) response pathways have been used as model systems to investigate both the signals involved and their organisation. Activated STAT1 diffuses freely in the cytoplasmic and nuclear compartments of the cell providing a ‘random walk’ element in the IFN-γ response. Completely foreign chimeric receptors and, remarkably, in the absence of STAT3, the endogenous IL-6 receptor can efficiently mediate an IFN-γ-like response. Accordingly all of the signals required for an IFN-γ response can be generated through physiological levels of a foreign ligand. JAK/STAT signalling, therefore, appears ‘soft-wired’, modular and highly flexible with substantial overlap between different response pathways. The data are consistent with a generic or ‘core’ set of signals from JAK/receptor complexes with ‘add-on’ modulation through specific receptor motifs. The cellular background likely profoundly affects the nature of the response.

【 授权许可】

Unknown