Interferon‐alpha‐induced phosphorylation and activation of cytosolic phospholipase A2 is required for the formation of interferon‐stimulated gene factor three

• Published in: The EMBO journal Vol. 15; no. 7; pp. 1566 - 1571
• Main Authors: Flati, V., Haque, S. J., Williams, B. R.
• Format: Journal Article
• Language: English
• Published: England 01-04-1996
• Subjects: Base Sequence; Cytosol - enzymology; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - metabolism; Enzyme Activation - drug effects; Gene Expression Regulation; HeLa Cells; Humans; Interferon-alpha - pharmacology; Interferon-gamma - pharmacology; Interferon-Stimulated Gene Factor 3; Interferon-Stimulated Gene Factor 3, gamma Subunit; Janus Kinase 1; Molecular Sequence Data; Mutation; Oligodeoxyribonucleotides - genetics; Phospholipases A - metabolism; Phospholipases A2; Phosphorylation; Protein-Tyrosine Kinases - metabolism; Recombinant Proteins; Signal Transduction; STAT1 Transcription Factor; Trans-Activators - metabolism; Transcription Factors - biosynthesis; Transcriptional Activation
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1002/j.1460-2075.1996.tb00501.x

Treatment of cells with interferon (IFN)‐alpha caused phosphorylation and activation of cytosolic phospholipase A2 (cPLA2). The protein tyrosine kinase Jak1 was found to be necessary for the activation of cPLA2. Jak1 could be co‐immunoprecipitated with cPLA2 from cell extracts, indicating that a close physical interaction occurs between these two proteins. The induction of IFN‐stimulated gene factor three (ISGF3) by IFN‐alpha, is blocked by cPLA2 inhibitors in cell cultures and in cell‐free reconstituted systems. However, these inhibitors do not block IFN‐alpha or gamma‐induced binding of STAT1 to the inverted repeat (IR) element of the IFN regulatory factor 1 (IRF‐1) gene. Thus, cPLA2 activations occurs as an early event in the IFN‐alpha response and is selectively involved in ISGF3‐dependent gene activation.