Section 41
Chapter 40,418

Induced factor binding to the interferon-stimulated response element. Interferon-alpha and platelet-derived growth factor utilize distinct signaling pathways

Hannigan, G.E.; Williams, B.R.

Journal of Biological Chemistry 266(14): 8765-8770


ISSN/ISBN: 0021-9258
PMID: 2026593
Accession: 040417345

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Interferon-alpha (IFN alpha) and platelet-derived growth factor (PDGF) each rapidly stimulate binding of nuclear factors from Balb/c 3T3 fibroblasts, to a 29-base pair regulatory sequence derived from the 5' upstream region of the murine 2-5A synthetase gene. This regulatory sequence contains a functional interferon-stimulated response element (ISRE) and also functions as a PDGF-responsive sequence. We show that IFN alpha induces binding of a protein of molecular mass 65 kDa to the ISRE. Constitutively expressed ISRE-binding proteins of 98 and 150 kDa are also demonstrated. Binding of inducible factors to the ISRE increases significantly within 15 min of IFN alpha or PDGF treatment. PDGF-induced binding is not mediated by IFN beta. The protein kinase inhibitors, staurosporine and K252a, block PDGF-induced ISRE binding and 2-5A synthetase gene expression. IFN alpha-induced ISRE binding and gene activation are not blocked by these inhibitors. Treatment of cells with 12-O-tetradecanoyl-13-acetate or dibutyryl cyclic AMP does not activate ISRE binding factors or 2-5A synthetase gene expression. PDGF responsiveness of the ISRE in vivo is also sensitive to staurosporine, indicating that inhibition of a protein kinase activity blocks the PDGF-specific transcriptional signal. Our data indicate the signal transduction pathway for IFN alpha-induced, ISRE-dependent transcription is distinct from the PDGF-induced ISRE response and is likely independent of cyclic AMP-dependent protein kinase and protein kinase C activities.

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