Interferonα activates NF-κB in JAK1-deficient cells through a TYK2-dependent pathway

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

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

In addition to activating members of the STAT transcription factor family, interferon α/β (IFNα/β) activates the NF-κB transcription factor. To determine the role of the Janus tyrosine kinase (JAK)-STAT pathway in NF-κB activation by IFN, we examined NF-κB activation in JAK1-deficient mutant human fibrosarcoma cells. In wild-type fibrosarcoma cells (2fTGH), IFN activates STAT1, STAT2, and STAT3, as well as NF-κB complexes comprised of p50 and p65. In contrast, in JAK1-deficient cells, IFN induces NF-κB activation and NF-κB 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-κB activation by IFN. Moreover, IFN does not promote NF-κB activation in TYK2-deficient mutant fibrosarcoma cells. Our results demonstrate a dichotomy between the classical JAK-STAT pathway and the NF-κB signaling pathway. In the IFN signaling pathway leading to STAT activation, both JAK1 and TYK2 are essential, whereas NF-κB activation requires only TYK2.

Original languageEnglish (US)
Pages (from-to)25849-25853
Number of pages5
JournalJournal of Biological Chemistry
Volume280
Issue number27
DOIs
StatePublished - Jul 8 2005

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Interferons
Chemical activation
Fibrosarcoma
Protein-Tyrosine Kinases
Janus Kinases
Transcription
TYK2 Kinase
STAT Transcription Factors
Genes
Transcription Factors
Cell Line
Cells
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Interferonα activates NF-κB in JAK1-deficient cells through a TYK2-dependent pathway. / Yang, Chuan; Murti, Aruna; Valentine, William J.; Du, Ziyun; Pfeffer, Lawrence.

In: Journal of Biological Chemistry, Vol. 280, No. 27, 08.07.2005, p. 25849-25853.

Research output: Contribution to journalArticle

Yang, Chuan ; Murti, Aruna ; Valentine, William J. ; Du, Ziyun ; Pfeffer, Lawrence. / Interferonα activates NF-κB in JAK1-deficient cells through a TYK2-dependent pathway. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 27. pp. 25849-25853.
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