Journal
MOLECULAR AND CELLULAR BIOLOGY
Volume 32, Issue 17, Pages 3382-3391Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.06331-11
Keywords
-
Categories
Funding
- Canadian Institutes of Health Research [MOP 44363]
- Canada Chair [950-216684]
- British Heart Foundation [PG/08/045/25069, CH/09/003]
- Wellcome Trust [075491/Z/04, GOA2008/16]
- Fonds Wetenschappelijk Onderzoek-Vlaanderen
- British Heart Foundation [RG/10/17/28553, PG/07/045/22690] Funding Source: researchfish
Ask authors/readers for more resources
In mammals, seven proprotein convertases (PCs) cleave secretory proteins after basic residues, and four of them are called furin-like PCs: furin, PC5, PACE4, and PC7. In vitro, they share many substrates. However, furin is essential during development since deficient embryos die at embryonic day 11 and exhibit multiple developmental defects, particularly defects related to the function of endothelial cells. To define the role of furin in endothelial cells, an endothelial cell-specific knockout (ecKO) of the Furin gene was generated. Newborns die shortly after birth, indicating that furin is essential in these cells. Magnetic resonance imaging revealed that ecKO embryos exhibit ventricular septal defects (VSD) and/or valve malformations. In addition, primary cultures of wild-type and ecKO lung endothelial cells revealed that ecKO cells are unable to grow. Growth was efficiently rescued by extracellular soluble furin. Analysis of the processing of precursors of endothelin-1 (ET-1), adrenomedullin (Adm), transforming growth factor beta 1 (TGF-beta 1), and bone morphogenetic protein 4 (BMP4) confirmed that ET-1, Adm, and TGF-beta 1 are in vivo substrates of endothelial furin. Mature ET-1 and BMP4 forms were reduced by similar to 90% in ecKO purified endothelial cells from lungs.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available