ENDOTHELIN STIMULATES SIS-INDUCING FACTOR-LIKE DNA-BINDING ACTIVITY IN CHO-K1 CELLS EXPRESSING ET(A) RECEPTORS

ET-1, a member of the family of peptides known as endothelins, binds t o a G-protein-coupled receptor, ET(A), and stimulates a variety of cel lular responses, including contraction, growth, and mitogenesis. ET-1 stimulation of a chinese hamster ovary cell line stably transfected wi th the ET(A) receptor (CHO/ET(A)) induced formation of SIF (sis-induci ng factor), a key component of the STAT (Signal Transducers and Activa tors of Transcription) pathway, in a concentration-dependent manner. S IF induction was blocked by a specific inhibitor of ET(A), BQ610, and by genistein, a tyrosine kinase inhibitor. This report demonstrates th at ET-1 stimulates the STAT pathway of signal transduction through a G -protein-coupled receptor, ET(A), in this stably transfected cell line . (C) 1996 Academic Press, Inc.