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
%0 Journal Article
%1 Joukov.1997
%A Joukov, V.
%A Sorsa, T.
%A Kumar, V.
%A Jeltsch, M.
%A Claesson-Welsh, L.
%A Cao, Y.
%A Saksela, O.
%A Kalkkinen, N.
%A Alitalo, K.
%D 1997
%J EMBO J.
%K Acid Amino Animals Antibodies C Cells Cos Cultured Data Dimerization Disulfides Endopeptidases Endothelial Endothelium Factor Factors Growth Humans Kinase Kinases Laboratories Molecular Phosphorylation Post-Translational Processing Protein Protein-Tyrosine Rabbits Receptor Receptors Research Sequence Tumor Tyrosine Vascular biosynthesis cells genetics metabolism secretion
%N 13
%P 3898-3911
%T Proteolytic processing regulates receptor specificity and activity of VEGF-C
%U PM:9233800
%V 16
%X 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
@article{Joukov.1997,
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 (K[D] = 135 pM) and VEGFR-2 (K[D] = 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 },
added-at = {2010-02-05T11:28:39.000+0100},
author = {Joukov, V. and Sorsa, T. and Kumar, V. and Jeltsch, M. and Claesson-Welsh, L. and Cao, Y. and Saksela, O. and Kalkkinen, N. and Alitalo, K.},
biburl = {https://www.bibsonomy.org/bibtex/251cf8a79aba5b8086354497c66a74926/kanefendt},
interhash = {94061caff2ac262a60622a6bc83370cb},
intrahash = {51cf8a79aba5b8086354497c66a74926},
journal = {EMBO J.},
keywords = {Acid Amino Animals Antibodies C Cells Cos Cultured Data Dimerization Disulfides Endopeptidases Endothelial Endothelium Factor Factors Growth Humans Kinase Kinases Laboratories Molecular Phosphorylation Post-Translational Processing Protein Protein-Tyrosine Rabbits Receptor Receptors Research Sequence Tumor Tyrosine Vascular biosynthesis cells genetics metabolism secretion},
number = 13,
pages = {3898-3911},
timestamp = {2010-02-05T11:28:47.000+0100},
title = {Proteolytic processing regulates receptor specificity and activity of VEGF-C},
url = {PM:9233800},
volume = 16,
year = 1997
}