Year: 1995
Type: article
Abstract: Proteolytic processing of the transforming growth factor beta precursor (pro-TGF beta) is an essential step in the formation of the biologically active TGF beta homodimeric protein (TGF beta). The 361-amino-acid precursor pro-TGF beta 1 has within its primary structure the R-H-R-R processing signal found in many constitutively secreted precursor proteins and potentially recognized by members of the mammalian convertase family of endoproteases. To determine whether cleavage of pro-TGF beta 1 can be achieved by the furin convertase in vitro, purified precursor was incubated in the presence of a truncated/secreted form of the enzyme. Immunoblots showed that the 55-kDa pro-TGF beta 1 was converted into the 44 and 12.5 kDa bands corresponding to the pro-region and the mature monomer, respectively. Treatment of pro-TGF beta 1 with furin resulted in a 5-fold increase in the production of biologically active TGF beta 1. Furthermore, when expressed in the furin-deficient LoVo cells, no processing of pro-TGF beta 1 was observed. In contrast, efficient processing was observed when pro-TGF beta was coexpressed with the furin convertase. Collectively, these results provide evidence that in our experimental systems the TGF beta 1 precursor is efficiently and correctly processed by human furin thus permitting release of the biologically active peptide.
Source: Journal of Biological Chemistry
Institutions: Université de Sherbrooke, University of Toledo Medical Center
Language: English
Topic: TGF-β signaling in diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
Award: G3005862381
OpenAlex ID: W1993531220