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 cel ls. These effects are mediated by two G-protein-coupled receptors and invol ve transcriptional regulation of growth-responsive and/or tissue-specific g enes. We have used the cardiac ANF promoter, which represents the best-stud ied tissue-specific endothelin target, to elucidate the nuclear pathways re sponsible for the transcriptional effects of endothelins. We found that car diac-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 reminiscen t of the well-characterized SRF-ternary complex factor interaction required for transcriptional induction of c-fos in response to growth factors. In t ransient cotransfections, GATA factors and SRF synergistically activate atr ial natriuretic factor and other ET-1-inducible promoters that contain both GATA and SRF binding sites. Thus, GATA factors may represent a new class o f tissue-specific SRF accessory factors that account for muscle- and other cell-specific SRF actions.