NDLI: Mutational switch of an IL-6 response to an interferon-gamma-like response.

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Mutational switch of an IL-6 response to an interferon-gamma-like response.

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Mutational switch of an IL-6 response to an interferon-gamma-like response.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Alonzi, Tonino Tininini, Silvia Strobl, Birgit Kerr, Ian M. Is'harc, Hayaatun Gesualdo, Ida Costa-pereira, Ana P. Schlaak, Joerg F. Poli, Valeria Newman, Sally J.
Description	Author Affiliation: Costa-Pereira AP ( Cancer Research United Kingdom London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom.);
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.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	12
Volume Number	99
Language	English
Publisher	National Academy of Sciences
Publisher Date	2002-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	DNA-Binding Proteins Genetics Interferon-gamma Immunology Interleukin-6 Physiology Trans-Activators Animals Cell Line Metabolism Fibroblasts Genes, MHC Class II Drug Effects Histocompatibility Antigens Class II Pharmacology Major Histocompatibility Complex Mice Recombinant Proteins STAT1 Transcription Factor STAT3 Transcription Factor Signal Transduction Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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