Serum response factor-GATA ternary complex required for nuclear signaling by a G-protein-coupled receptor.
Endothelins are a family of biologically active peptides that are critical for development and function of neural crest-derived and cardiovascular cells. These effects are mediated by two G-protein-coupled receptors and involve transcriptional regulation of growth-responsive and/or tissue-specific genes. We have used the cardiac ANF promoter, which represents the best-studied tissue-specific endothelin target, to elucidate the nuclear pathways responsible for the transcriptional effects of endothelins. We found that cardiac-specific response to endothelin 1 (ET-1) requires the combined action of the serum response factor (SRF) and the tissue-restricted GATA proteins which bind over their adjacent sites, within a 30-bp ET-1 response element. We show that SRF and GATA proteins form a novel ternary complex reminiscent of the well-characterized SRF-ternary complex factor interaction required for transcriptional induction of c-fos in response to growth factors. In transient cotransfections, GATA factors and SRF synergistically activate atrial natriuretic factor and other ET-1-inducible promoters that contain both GATA and SRF binding sites. Thus, GATA factors may represent a new class of tissue-specific SRF accessory factors that account for muscle- and other cell-specific SRF actions.
Morin
S
S
Laboratoire de Développment et Différenciation Cardiaques, Institut de Recherches Cliniques de Montréal, Université de Montréal, Montreal, Quebec, Canada.
Paradis
P
P
Aries
A
A
Nemer
M
M
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D019332:Endothelin-1 / Q000494:pharmacology; D050991:GATA4 Transcription Factor; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D046911:Macromolecular Substances; D009206:Myocardium / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051381:Rats; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017466:Receptors, Endothelin / Q000378:metabolism; D026362:Serum Response Factor; D015398:Signal Transduction; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*
D017931:DNA Primers; D004268:DNA-Binding Proteins; D019332:Endothelin-1; D050991:GATA4 Transcription Factor; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D011956:Receptors, Cell Surface; D017466:Receptors, Endothelin; D026362:Serum Response Factor; D014157:Transcription Factors; D009320:Atrial Natriuretic Factor; D019204:GTP-Binding Proteins