Research Institute , Hospital for Sick Children , Toronto , Canada .
J Biol Chem 266 : 8765-70 ( 1991)
Abstract
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 -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 .