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Volume 270, Number 18, Issue of May 5, pp. 10618-10624, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
Processing of Transforming Growth Factor 1 Precursor by Human Furin Convertase

Claire M. Dubois , Marie-Hélène Laprise , Franois Blanchette , Larry E. Gentry , Richard Leduc

Proteolytic processing of the transforming growth factor precursor (pro-TGF) is an essential step in the formation of the biologically active TGF homodimeric protein (TGF). The 361-amino-acid precursor pro-TGF1 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-TGF1 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-TGF1 was converted into the 44 and 12.5 kDa bands corresponding to the pro-region and the mature monomer, respectively. Treatment of pro-TGF1 with furin resulted in a 5-fold increase in the production of biologically active TGF1. Furthermore, when expressed in the furin-deficient LoVo cells, no processing of pro-TGF1 was observed. In contrast, efficient processing was oberved when pro-TGF was coexpressed with the furin convertase. Collectively, these results provide evidence that in our experimental systems the TGF1 precursor is efficiently and correctly processed by human furin thus permitting release of the biologically active peptide.



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Cross-talk between the p42/p44 MAP Kinase and Smad Pathways in Transforming Growth Factor beta 1-induced Furin Gene Transactivation
J. Biol. Chem., August 31, 2001; 276(36): 33986 - 33994.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
A.-M. Khatib, G. Siegfried, A. Prat, J. Luis, M. Chretien, P. Metrakos, and N. G. Seidah
Inhibition of Proprotein Convertases Is Associated with Loss of Growth and Tumorigenicity of HT-29 Human Colon Carcinoma Cells. IMPORTANCE OF INSULIN-LIKE GROWTH FACTOR-1 (IGF-1) RECEPTOR PROCESSING IN IGF-1-MEDIATED FUNCTIONS
J. Biol. Chem., August 10, 2001; 276(33): 30686 - 30693.
[Abstract] [Full Text] [PDF]


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