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Molecular and Cellular Biology, February 2001, p. 1036-1044, Vol. 21, No. 4
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.4.1036-1044.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Serum Response Factor-GATA Ternary Complex Required for Nuclear Signaling by a G-Protein-Coupled Receptor

Steves Morin,1,2 Pierre Paradis,1 Anne Aries,1 and Mona Nemer1,2,3,*

Laboratoire de Développment et Différenciation Cardiaques, Institut de Recherches Cliniques de Montréal,1 and Programme de Biologie Moléculaire2 and Départment de Pharmacologie,3 Université de Montréal, Montreal, Quebec, Canada

Received 11 August 2000/Returned for modification 18 September 2000/Accepted 9 November 2000

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.

* Corresponding author. Mailing address: Institut de recherches cliniques de Montréal, Laboratoire de développement et différenciation cardiaques, 110 des Pins Ouest, Montréal, Quebec, Canada H2W 1R7. Phone: (514) 987-5680. Fax: (514) 987-5575. E-mail: nemerm{at}ircm.qc.ca.

Molecular and Cellular Biology, February 2001, p. 1036-1044, Vol. 21, No. 4
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.4.1036-1044.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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