Transforming growth factor-β (TGF-β) shows a variety of biological activities in various organs or cells. Recently some factors such as Smads (Sma and Mad proteins) and TGF-β activating kinase 1 (‘TAK1’) have been characterized as signalling molecules downstream of TGF-β. Several TGF-β response elements have been identified such as cAMP response element, Smad binding element, and recognition sites for activating protein-1 and stimulating protein-1 in various gene promoters. We also reported a TGF-β response element in the human C-type natriuretic peptide (CNP) gene promoter. In this paper, we report on a novel factor which regulates the TGF-β response promoter. This factor, named TSF1 (TGF-β stimulated factor 1), possessed DNA-binding ability and activated the TGF-β responsive CNP promoter or vascular endothelial growth factor gene promoter which possesses a sequence element analogous to the TGF-β responsive GC-rich element of the CNP promoter. TSF1 did not directly activate a Smads-dependent promoter from plasminogen activator inhibitor 1 gene, but it showed enhancement in co-operation with Smad3 and Smad4. Interestingly, this factor had the structural features of a Ser/Thr kinase and actually exhibited protein kinase activity. TSF1 mRNA as well as its protein level were stimulated by TGF-β treatment. Thus, TSF1 is an unique factor with two biological functions, transcriptional regulation and protein phosphorylation, that may be involved in TGF-β signals.
The nucleotide sequence data reported for the rat, mouse and human will appear in DDBJ, EMBL, GenBank® and GSDB Nucleotide Sequence Databases under the accession numbers D86220, AB022179 and AB020739 respectively.