Requirement of catalytically active Tyk2 and accessory signals for the induction of TRAIL mRNA by IFN-beta.
J Interferon Cytokine Res
; 27(9): 767-79, 2007 Sep.
Article
en En
| MEDLINE
| ID: mdl-17892398
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand/Apo2 ligand (TRAIL/Apo2L) mRNA was induced preferentially by interferon (IFN)-beta but not IFN-alpha in human fibrosarcoma and primary fibroblast cells. To characterize the signaling components mediating the IFN subtype-specific induction of this gene, we used mutant cell lines lacking individual components involved in signaling by type I IFNs. TRAIL was not induced by IFN-beta in mutant cell lines U2A, U3A, U4A, U5A, and U6A, which lack, respectively, IFN regulatory factor-9 (IRF-9), Stat1, Jak1, IFNAR-2.2, and Stat2, indicating transcription factor IFN-stimulated gene factor 3 (ISGF3) was essential for the induction of this gene. TRAIL was not induced by IFN-beta in U1A (Tyk2 null) or U1A.R930 cells (that express a kinase-deficient point mutant of Tyk2) but was induced in U1A.wt-5 cells (U1A cells expressing wild-type Tyk2), indicating that Tyk2 protein and kinase activity were both required for induction of the gene. Biochemical and genetic analyses revealed the requirement of transcription factor NF-kappa B and phosphoinositide 3-kinase (PI3K) but not extracellular signal-regulated kinase (ERK) for the induction of TRAIL by IFN-beta. Furthermore, the antiproliferative but not antiviral effects of IFN-beta required catalytically active Tyk2, suggesting that expression of genes, such as TRAIL, may play an important role in mediating the biologic effects of IFNs.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Interferón beta
/
TYK2 Quinasa
/
Ligando Inductor de Apoptosis Relacionado con TNF
Límite:
Humans
Idioma:
En
Revista:
J Interferon Cytokine Res
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos