Proteolytic processing regulates receptor specificity and activity of VEGF-C. Joukov, V., Sorsa, T., Kumar, V., Jeltsch, M., Claesson-Welsh, L., Cao, Y., Saksela, O., Kalkkinen, N., & Alitalo, K. EMBO Journal, 16(13):3898–3911, July, 1997.
Proteolytic processing regulates receptor specificity and activity of VEGF-C [link]Paper  doi  abstract   bibtex   
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 = 135 pM) and VEGFR-2 (KD = 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 homodimers. These data implicate proteolytic processing as a regulator of VEGF-C activity, and reveal novel structure–function relationships in the PDGF/VEGF family.
@article{joukov_proteolytic_1997,
	title = {Proteolytic processing regulates receptor specificity and activity of {VEGF}-{C}},
	volume = {16},
	copyright = {© 1997 Nature Publishing Group},
	url = {http://dx.doi.org/10.1093/emboj/16.13.3898},
	doi = {10.1093/emboj/16.13.3898},
	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 = 135 pM) and VEGFR-2 (KD = 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 homodimers. These data implicate proteolytic processing as a regulator of VEGF-C activity, and reveal novel structure–function relationships in the PDGF/VEGF family.},
	language = {en},
	number = {13},
	urldate = {2012-08-22},
	journal = {EMBO Journal},
	author = {Joukov, Vladimir and Sorsa, Tarja and Kumar, Vijay and Jeltsch, Michael and Claesson-Welsh, Lena and Cao, Yihai and Saksela, Olli and Kalkkinen, Nisse and Alitalo, Kari},
	month = jul,
	year = {1997},
	keywords = {VEGF, VEGF-C, angiogenesis, growth factor, proteolytic processing},
	pages = {3898--3911},
}

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