STRUCTURE AND EXPRESSION OF THE PROMOTER FOR THE R4 ALK5 HUMAN TYPE-ITRANSFORMING GROWTH-FACTOR-BETA RECEPTOR - REGULATION BY TGF-BETA/

The type I transforming growth factor-beta (TGF-beta) receptors are se rine/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 analysi s indicates that the promoter lacks a TATA and CAAT box but is highly GC-rich and contains putative Sp1 binding sites. The transcriptional s tart site is approx. 232 base pairs upstream of the AUG start codon. I n human lung fibroblasts, TGF-beta induced a 3-fold increase in steady -state level for type I receptor mRNA. Exposure of cells transfected w ith a 618 bp promoter fragment to TGF-beta 1 up-regulated transcriptio nal activity indicating that a TGF-beta response element is contained within this region.