title: Differential regulation of c-fos gene expression by two types of human endothelin receptor in Chinese hamster ovary cells.
abstract: To investigate the nuclear signalling pathway induced by endothelin (ET) isopeptides, we have established permanent Chinese hamster ovary (CHO) cell lines, CHO-ETA/fos-lacZ and CHO-ETB/fos-lacZ, that produce both a c-fos-beta-galactosidase fusion protein and either the type A or the type B human ET receptor. These cell lines permitted a colorimetric measurement of c-fos expression, which was induced by the signal transduction system with ET receptors and ET isopeptides. We found that the ET-1-dependent c-fos expression was so efficient that it could respond to low concentrations (even a physiological concentration) of ET-1. For example, CHO-ETA/fos-lacZ and CHO-ETB/fos-lacZ responded to ET concentrations of 5 x 10(-9) M and 5 x 10(-13) M respectively. Using this highly sensitive system, the H-7 sensitive protein kinase was found to be involved in signal transduction mediated by ETA, and also partly in the ETB-mediated pathway. These lines of evidence suggest that c-fos expression occurs through at least two different pathways, depending on the concentration of ET in plasma.
authors.affiliation: Department of Molecular Genetics, Nippon Roche Research Center, Kanagawa prefecture, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tabuchi
authors.forename: Y
authors.initials: Y
authors.lastname: Furuichi
authors.forename: C
authors.initials: C
authors.lastname: Miyamoto
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D016466:CHO Cells / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D016232:Endothelins / Q000502:physiology*; D005786:Gene Expression Regulation; D016762:Genes, fos; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D017466:Receptors, Endothelin / Q000145:classification / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection
chemical_list: D016232:Endothelins; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D017466:Receptors, Endothelin; D011993:Recombinant Fusion Proteins; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine