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- Title
Proteolytic processing regulates receptor specificity and activity of VEGF-C.
- Authors
Joukov, Vladimir; Sorsa, Tarja; Kumar, Vijay; Jeltsch, Michael; Claesson-Welsh, Lena; Yihai Cao; Saksela, Olli; Kalkkinen, Nisse; Alitalo, Kari
- Abstract
The recently identified vascular endothelial growth factor C (VEGF-C) belongs to the platelet-derived growth factor (PDGF)/VEGF family of growth factors and is a ligand for the endothelial-specific receptor tyrosine kinases VEGFR-3 and VEGFR-2. The VEGF homology domain spans only about one-third of the cysteine-rich VEGF-C precursor. Here we have analysed the role of post-translational processing in VEGF-C secretion and function, as well as the structure of the mature VEGF-C. The stepwise proteolytic processing of VEGF-C generated several VEGF-C forms with increased activity towards VEGFR-3, but only the fully processed VEGF-C could activate VEGFR-2. Recombinant ‘mature’ VEGF-C made in yeast bound VEGFR-3 (KD J 135 pM) and VEGFR-2 (KD J 410 pM) and activated these receptors. Like VEGF, mature VEGF-C increased vascular permeability, as well as the migration and proliferation of endothelial cells. Unlike other members of the PDGF/VEGF family, mature VEGF-C formed mostly non-covalent homo-dimers. These data implicate proteolytic processing as a regulator of VEGF-C activity, and reveal novel structure-function relationships in the PDGF/VEGF family.
- Subjects
VASCULAR endothelial growth factors; LIGANDS (Biochemistry); PROTEIN-tyrosine kinases; HOMOLOGY (Biology); NEOVASCULARIZATION; PROTEOLYSIS
- Publication
EMBO Journal, 1997, Vol 16, Issue 13, p3898
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1093/emboj/16.13.3898