@article {13,
	title = {Genomic organization of human and mouse genes for vascular endothelial growth factor C},
	journal = {J Biol Chem},
	volume = {272},
	year = {1997},
	month = {1997/Oct/},
	pages = {25176 - 83},
	abstract = {We report here the cloning and characterization of human and mouse genes for vascular endothelial growth factor C (VEGF-C), a newly isolated member of the vascular endothelial growth factor/platelet-derived growth factor (VEGF/PDGF) family. Both VEGF-C genes comprise over 40 kilobase pairs of genomic DNA and consist of seven exons, all containing coding sequences. The VEGF homology domain of VEGF-C is encoded by exons 3 and 4. Exons 5 and 7 encode cysteine-rich motifs of the type C6C10CRC, and exon 6 encodes additional C10CXCXC motifs typical of a silk protein. A putative alternatively spliced rare RNA form lacking exon 4 was identified in human fibrosarcoma cells, and a major transcription start site was located in the human VEGF-C gene 523 base pairs upstream of the translation initiation codon. The upstream promoter sequences contain conserved putative binding sites for Sp-1, AP-2, and NF-kappaB transcription factors but no TATA box, and they show promoter activity when transfected into cells. The VEGF-C gene structure is thus assembled from exons encoding propeptides and distinct cysteine-rich domains in addition to the VEGF homology domain, and it shows both similarities and distinct differences in comparison with other members of the VEGF/PDGF gene family.},
	url = {http://view.ncbi.nlm.nih.gov/pubmed/9312130},
	author = {Chilov, D and Kukk, E and Taira, S and Jeltsch, M and Kaukonen, J and Palotie, A and Joukov, V and Alitalo, K}
}
@article {10,
	title = {Hyperplasia of lymphatic vessels in VEGF-C transgenic mice},
	journal = {Science (80- )},
	volume = {276},
	year = {1997},
	month = {1997/May/},
	pages = {1423 - 5},
	abstract = {No growth factors specific for the lymphatic vascular system have yet been described. Vascular endothelial growth factor (VEGF) regulates vascular permeability and angiogenesis, but does not promote lymphangiogenesis. Overexpression of VEGF-C, a ligand of the VEGF receptors VEGFR-3 and VEGFR-2, in the skin of transgenic mice resulted in lymphatic, but not vascular, endothelial proliferation and vessel enlargement. Thus, VEGF-C induces selective hyperplasia of the lymphatic vasculature, which is involved in the draining of interstitial fluid and in immune function, inflammation, and tumor metastasis. VEGF-C may play a role in disorders involving the lymphatic system and may be of potential use in therapeutic lymphangiogenesis.},
	url = {http://view.ncbi.nlm.nih.gov/pubmed/9162011},
	author = {Jeltsch, M and Kaipainen, A and Joukov, V and Meng, X and Lakso, M and Rauvala, H and Swartz, M and Fukumura, D and Jain, R K and Alitalo, K}
}
@article {14,
	title = {Proteolytic processing regulates receptor specificity and activity of VEGF-C},
	journal = {EMBO J},
	volume = {16},
	year = {1997},
	month = {1997/Jul/},
	pages = {3898 - 911},
	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 {\textquoteright}mature{\textquoteright} 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 homodimers. These data implicate proteolytic processing as a regulator of VEGF-C activity, and reveal novel structure-function relationships in the PDGF/VEGF family.},
	url = {http://view.ncbi.nlm.nih.gov/pubmed/9233800},
	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}
}
@article {12,
	title = {Vascular endothelial growth factors VEGF-B and VEGF-C},
	journal = {J Cell Physiol},
	volume = {173},
	year = {1997},
	month = {1997/Nov/},
	pages = {211 - 5},
	url = {http://view.ncbi.nlm.nih.gov/pubmed/9365524},
	author = {Joukov, V and Kaipainen, A and Jeltsch, M and Pajusola, K and Olofsson, B and Kumar, V and Eriksson, U and Alitalo, K}
}
@article {9,
	title = {VEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a role in lymphatic vascular development},
	journal = {Development},
	volume = {122},
	year = {1996},
	month = {1996/Dec/},
	pages = {3829 - 37},
	abstract = {The vascular endothelial growth factor family has recently been expanded by the isolation of two new VEGF-related factors, VEGF-B and VEGF-C. The physiological functions of these factors are largely unknown. Here we report the cloning and characterization of mouse VEGF-C, which is produced as a disulfide-linked dimer of 415 amino acid residue polypeptides, sharing an 85\% identity with the human VEGF-C amino acid sequence. The recombinant mouse VEGF-C protein was secreted from transfected cells as VEGFR-3 (Flt4) binding polypeptides of 30-32x10(3) Mr and 22-23x10(3) Mr which preferentially stimulated the autophosphorylation of VEGFR-3 in comparison with VEGFR-2 (KDR). In in situ hybridization, mouse VEGF-C mRNA expression was detected in mesenchymal cells of postimplantation mouse embryos, particularly in the regions where the lymphatic vessels undergo sprouting from embryonic veins, such as the perimetanephric, axillary and jugular regions. In addition, the developing mesenterium, which is rich in lymphatic vessels, showed strong VEGF-C expression. VEGF-C was also highly expressed in adult mouse lung, heart and kidney, where VEGFR-3 was also prominent. The pattern of expression of VEGF-C in relation to its major receptor VEGFR-3 during the sprouting of the lymphatic endothelium in embryos suggests a paracrine mode of action and that one of the functions of VEGF-C may be in the regulation of angiogenesis of the lymphatic vasculature.},
	url = {http://view.ncbi.nlm.nih.gov/pubmed/9012504},
	author = {Kukk, E and Lymboussaki, A and Taira, S and Kaipainen, A and Jeltsch, M and Joukov, V and Alitalo, K}
}
