The Suppressor of Cytokine Signaling (SOCS) 1 and SOCS3 but Not SOCS2 Proteins Inhibit Interferon-mediated Antiviral and Antiproliferative Activities*
- From the Departments of ‡Medicine and¶Biological Chemistry, Molecular Biology Institute, University of California, Los Angeles, California 90095
Abstract
The suppressor of cytokine signaling (SOCS) proteins are a family of cytokine-inducible negative regulators of cytokine signaling. Interferon (IFN)-γ treatment induces the expression of SOCS1, SOCS2, and SOCS3 mRNAs. To examine the effect of SOCS proteins on IFN-mediated Janus-activated kinase/signal transducers and activators of transcription (STAT) signaling, HeLa- and MCF-7-derived stable cell lines expressing SOCS1, SOCS2, and SOCS3 proteins were established. SOCS1 and SOCS3 but not SOCS2 inhibited the tyrosine phosphorylation and nuclear translocation of STAT1 in response to IFN stimulation. The IFN-mediated antiviral and antiproliferative activities were consistently blocked by the constitutive expression of SOCS1 and SOCS3 but not SOCS2 proteins. The maximum inhibitory activities of SOCS1 and SOCS3 proteins toward the activation of STAT1 were observed at very low levels of SOCS protein expression. In addition, SOCS1 exhibited a much stronger inhibitory activity toward the activation of STAT1 than did SOCS3. These results suggest that SOCS1 and SOCS3 but not SOCS2 are inhibitors of IFN-mediated Janus-activated kinase/STAT signaling pathways.
Footnotes
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↵* This study was supported by funds from the California Breast Cancer Research Program of the University of California (1KB-0224) and Grant 4346 from the Council for Tobacco Research, USA (to K. S.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵§ A STAR (Subspecialty Training and Advanced Research) fellow in the Department of Medicine at the University of California, Los Angeles.
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↵‖ To whom correspondence should be addressed: Division of Hematology-Oncology, 11-934 Factor Bldg., 10833 LeConte Ave., Los Angeles, CA 90095-1678. Tel.: 310-206-9168; Fax: 310-825-6192; E-mail:Kshuai{at}mednet.ucla.edu.
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↵2 M. M. Song and K. Shuai, unpublished data.
- Abbreviations:
- IFN
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interferon
- SOCS
-
suppressor of cytokine signaling
- Jak
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Janus-activated kinase
- STAT
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signal transducers and activators of transcription
- VSV
-
vesicular stomatitis virus
- IL
-
interleukin
- OM
-
oncostatin M.
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- Received July 7, 1998.
- Revision received September 21, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
