Structure and expression of the promoter for the R4/ALK5 human type I transforming growth factor-beta receptor: regulation by TGF-beta.
The type I transforming growth factor-beta (TGF-beta) receptors are serine/threonine kinases that are essential for the action of TGF-beta. In this paper, we describe the molecular cloning and expression of the R4/ALK5 human type I TGF-beta receptor promoter. DNA sequence analysis indicates that the promoter lacks a TATA and CAAT box but is highly GC-rich and contains putative Sp1 binding sites. The transcriptional start site is approx. 232 base pairs upstream of the AUG start codon. In human lung fibroblasts, TGF-beta induced a 3-fold increase in steady-state level for type I receptor mRNA. Exposure of cells transfected with a 618 bp promoter fragment to TGF-beta 1 up-regulated transcriptional activity indicating that a TGF-beta response element is contained within this region.
Bloom
B B
BB
Pulmonary Center, Boston University School of Medicine, MA 02118, USA.
Humphries
D E
DE
Kuang
P P
PP
Fine
A
A
Goldstein
R H
RH
D030201:Activin Receptors, Type I; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D005347:Fibroblasts; D005786:Gene Expression Regulation / Q000187:drug effects*; D015698:Genomic Library; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis; D008168:Lung / Q000378:metabolism; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis; D015183:Restriction Mapping; D014158:Transcription, Genetic; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D001616:beta-Galactosidase / Q000096:biosynthesis
D017931:DNA Primers; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D008156:Luciferases; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human; D001616:beta-Galactosidase