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J. Biol. Chem., Vol. 280, Issue 27, 25849-25853, July 8, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/27/25849    most recent M413721200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yang, C. H. Articles by Pfeffer, L. M. Search for Related Content PubMed PubMed Citation Articles by Yang, C. H. Articles by Pfeffer, L. M. Social Bookmarking                      What's this?

Interferon Activates NF-B in JAK1-deficient Cells through a TYK2-dependent Pathway^*

Chuan He Yang, Aruna Murti, William J. Valentine, Ziyun Du, and Lawrence M. Pfeffer

From the Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center and the University of Tennessee Cancer Institute, Memphis, Tennessee 38163

In addition to activating members of the STAT transcription factor family, interferon / (IFN/) activates the NF-B transcription factor. To determine the role of the Janus tyrosine kinase (JAK)-STAT pathway in NF-B activation by IFN, we examined NF-B activation in JAK1-deficient mutant human fibrosarcoma cells. In wild-type fibrosarcoma cells (2fTGH), IFN activates STAT1, STAT2, and STAT3, as well as NF-B complexes comprised of p50 and p65. In contrast, in JAK1-deficient cells, IFN induces NF-B activation and NF-B dependent gene transcription but does not activate these STAT proteins and has no effect on STAT-dependent gene transcription. Expression of a catalytically inactive TYK2 tyrosine kinase in JAK1-deficient cells, as well as in the highly IFN-sensitive Daudi lymphoblastoid cell line, abrogates NF-B activation by IFN. Moreover, IFN does not promote NF-B activation in TYK2-deficient mutant fibrosarcoma cells. Our results demonstrate a dichotomy between the classical JAK-STAT pathway and the NF-B signaling pathway. In the IFN signaling pathway leading to STAT activation, both JAK1 and TYK2 are essential, whereas NF-B activation requires only TYK2.

Received for publication, December 6, 2004 , and in revised form, May 5, 2005.

^* This work was supported by National Institute of Health Grant CA73753 (to L. M. P). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, 930 Madison Ave., Rm. 530, Memphis, TN 38163. Tel.: 901-448-7855; Fax: 901-448-6979; E-mail: lpfeffer{at}utmem.edu

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