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

Abstract

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.