%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 }