Direct association of STAT3 with the IFNAR-1 chain of the human type I interferon receptor

Chuan Yang, Wei Shi, Leela Basu, Aruna Murti, Stefan N. Constantinescu, Lawrence Blatt, Ed Croze, Jerald E. Mullersman, Lawrence Pfeffer

Research output: Contribution to journalArticle

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Abstract

Based on the reports of the activation of the transcription factor known as STAT3 (for signal transducers and activators of transcription) or APRF (for acute phase response factor) by various cytokines, we investigated the possible role of STAT3 in type I interferon (IFN) receptor signaling. We show that STAT3 undergoes IFNα-dependent tyrosine phosphorylation and IFNα treatment induces protein-DNA complexes that contain STAT3. In addition, STAT3 associates with the IFNAR-1 chain of the type I receptor in a tyrosine phosphorylation-dependent manner upon IFNα addition. The binding of STAT3 to the IFNAR-1 chain occurs through a direct interaction between the SH2 domain- containing portion of STAT3 and the tyrosine-phosphorylated IFNAR-1 chain. Furthermore, tyrosine-phosphorylated STAT3 bound to the IFNAR-1 chain also undergoes a secondary modification involving serine phosphorylation. This phosphorylation event is apparently mediated by protein kinase C, since it was blocked by low concentrations of the protein kinase inhibitor H-7. The biological relevance of IFN activation of STAT3 is further illustrated by the finding that STAT3 is not activated by IFN in a cell line resistant to the antiviral and antiproliferative actions of IFNα but in which other components of the JAK-STAT pathway are activated by IFNα.

Original languageEnglish (US)
Pages (from-to)8057-8061
Number of pages5
JournalJournal of Biological Chemistry
Volume271
Issue number14
DOIs
StatePublished - Apr 5 1996

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Interferons
Association reactions
Phosphorylation
Tyrosine
Chemical activation
Interferon alpha-beta Receptor
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
STAT3 Transcription Factor
src Homology Domains
Transcription
Protein Kinase Inhibitors
human IFNAR2 protein
Transducers
Serine
Protein Kinase C
Antiviral Agents
Transcription Factors
Cells
Cytokines
Cell Line

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Direct association of STAT3 with the IFNAR-1 chain of the human type I interferon receptor. / Yang, Chuan; Shi, Wei; Basu, Leela; Murti, Aruna; Constantinescu, Stefan N.; Blatt, Lawrence; Croze, Ed; Mullersman, Jerald E.; Pfeffer, Lawrence.

In: Journal of Biological Chemistry, Vol. 271, No. 14, 05.04.1996, p. 8057-8061.

Research output: Contribution to journalArticle

Yang, C, Shi, W, Basu, L, Murti, A, Constantinescu, SN, Blatt, L, Croze, E, Mullersman, JE & Pfeffer, L 1996, 'Direct association of STAT3 with the IFNAR-1 chain of the human type I interferon receptor', Journal of Biological Chemistry, vol. 271, no. 14, pp. 8057-8061. https://doi.org/10.1074/jbc.271.14.8057
Yang, Chuan ; Shi, Wei ; Basu, Leela ; Murti, Aruna ; Constantinescu, Stefan N. ; Blatt, Lawrence ; Croze, Ed ; Mullersman, Jerald E. ; Pfeffer, Lawrence. / Direct association of STAT3 with the IFNAR-1 chain of the human type I interferon receptor. In: Journal of Biological Chemistry. 1996 ; Vol. 271, No. 14. pp. 8057-8061.
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