Abstract:
:Signaling through Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) is central to the responses to the majority of cytokines and some growth factors, including the interferons (IFNs) and the IL-6 family of cytokines. The biological responses to stimulation through the widely distributed IL-6 and IFN-gamma receptors are, however, completely different. Remarkably, it is shown here that, in mouse embryo fibroblasts lacking STAT3, IL-6 mediates an IFN-gamma-like response including prolonged activation of STAT1, the induction of multiple IFN-gamma-inducible genes, the expression of class II MHC antigens, and an antiviral state. Normal cells exposed to IL-6 thus require a STAT3-dependent function(s) to down-regulate STAT1 activity and prevent an IFN-gamma-like response. The data encourage the view that the very disparate IFN-gamma and IL-6 JAK/receptor complexes mediate a common set of generic or "core" signals which are subject to STAT3-dependent modulation to provide IL-6 specificity. The switching of one cytokine response to one closely mimicking another as a result of the loss of a single signaling component has profound implications, for example, for the interpretation of the phenotypes of knockout mice and for the clinical use of inhibitors of signaling.
journal_name
Proc Natl Acad Sci U S Aauthors
Costa-Pereira AP,Tininini S,Strobl B,Alonzi T,Schlaak JF,Is'harc H,Gesualdo I,Newman SJ,Kerr IM,Poli Vdoi
10.1073/pnas.122236099keywords:
subject
Has Abstractpub_date
2002-06-11 00:00:00pages
8043-7issue
12eissn
0027-8424issn
1091-6490pii
99/12/8043journal_volume
99pub_type
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