Structure and expression of the promoter for the R4/ALK5 human type I transforming growth factor-β receptor: regulation by TGF-β

• Published in: Biochimica et biophysica acta 1996-07, Vol.1312 (3), p.243-248
• Main Authors: Bloom, Brian B., Humphries, Donald E., Kuang, Ping-Ping, Fine, Alan, Goldstein, Ronald H.
• Format: Article
• Language: English
• Subjects: Activin Receptors, Type I; Base Sequence; beta-Galactosidase - biosynthesis; Cell Line; DNA Primers; Fibroblasts; Gene Expression Regulation - drug effects; Genomic Library; Human lung fibroblast; Humans; Luciferases - biosynthesis; Lung - metabolism; Molecular Sequence Data; Polymerase Chain Reaction; Promoter; Promoter Regions, Genetic; Protein-Serine-Threonine Kinases - biosynthesis; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Receptor; Receptor, Transforming Growth Factor-beta Type I; Receptors, Transforming Growth Factor beta - biosynthesis; Receptors, Transforming Growth Factor beta - genetics; Recombinant Proteins - biosynthesis; Restriction Mapping; Transcription, Genetic; Transfection; Transforming Growth Factor beta - pharmacology; Transforming growth factor-β
• ISSN: 0167-4889; 0006-3002; 1879-2596
• DOI: 10.1016/0167-4889(96)00043-2

The type I transforming growth factor-β (TGF-β) receptors are serine/threonine kinases that are essential for the action of TGF-β. In this paper, we describe the molecular cloning and expression of the R4/ALK5 human type I TGF-β receptor promoter. DNA sequence analysis indicates that the promoter lacks a TATA and CAAT box but is highly GC-rich and contains putative Spl binding sites. The transcriptional start site is approx. 232 base pairs upstream of the AUG start codon. In human lung fibroblasts, TGF-β induced a 3-fold increase in steady-state level for type I receptor mRNA. Exposure of cells transfected with a 618 by promoter fragment to TGF-β1 up-regulated transcriptional activity indicating that a TGF-β response element is contained within this region.