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PMID: 8617204 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases.

The EMBO journal ·Vol. 15 ·No. 2 ·1996-01-15 ·Pages 290-98

Joukov V, Pajusola K, Kaipainen A, Chilov D, Lahtinen I, Kukk E, Saksela O, Kalkkinen N, Alitalo K

Abstract

Angiogenesis, the sprouting of new blood vessels from pre-existing ones, and the permeability of blood vessels are regulated by vascular endothelial growth factor (VEGF) via its two known receptors Flt1 (VEGFR-1) and KDR/Flk-1 (VEGFR-2). The Flt4 receptor tyrosine kinase is related to the VEGF receptors, but does not bind VEGF and its expression becomes restricted mainly to lymphatic endothelia during development. In this study, we have purified the Flt4 ligand, VEGF-C, and cloned its cDNA from human prostatic carcinoma cells. While VEGF-C is homologous to other members of the VEGF/platelet derived growth factor (PDGF) family, its C-terminal half contains extra cysteine-rich motifs characteristic of a protein component of silk produced by the larval salivary glands of the midge, Chironomus tentans. VEGF-C is proteolytically processed, binds Flt4, which we rename as VEGFR-3 and induces tyrosine autophosphorylation of VEGFR-3 and VEGFR-2. In addition, VEGF-C stimulated the migration of bovine capillary endothelial cells in collagen gel. VEGF-C is thus a novel regulator of endothelia, and its effects may extend beyond the lymphatic system, where Flt4 is expressed.

MeSH Terms
3T3 Cells Amino Acid Sequence Animals Base Sequence Blotting, Northern Capillaries Cattle Cell Line Chironomidae Cloning, Molecular Consensus Sequence Cysteine DNA Primers Endothelial Growth Factors/biosynthesis,chemistry,metabolism Endothelium, Vascular/cytology,physiology Enzyme Activation Gene Expression Growth Substances/chemistry Humans Male Mice Molecular Sequence Data Platelet-Derived Growth Factor/chemistry Prostatic Neoplasms Receptor Protein-Tyrosine Kinases/biosynthesis,metabolism Receptors, Cell Surface/biosynthesis,metabolism Receptors, Growth Factor/metabolism Receptors, Vascular Endothelial Growth Factor Recombinant Proteins/biosynthesis,metabolism Salivary Glands/metabolism Sequence Homology, Amino Acid Spodoptera Transfection Tumor Cells, Cultured Vascular Endothelial Growth Factor C Vascular Endothelial Growth Factor Receptor-3
Chemicals
DNA Primers Endothelial Growth Factors Growth Substances Platelet-Derived Growth Factor Receptors, Cell Surface Receptors, Growth Factor Recombinant Proteins Vascular Endothelial Growth Factor C Receptor Protein-Tyrosine Kinases Receptors, Vascular Endothelial Growth Factor Vascular Endothelial Growth Factor Receptor-3 Cysteine
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Joukov V
Department of Virology, Haartman Institute, University of Helinski, Finland.
Pajusola K
Kaipainen A
Chilov D
Lahtinen I
Kukk E
Saksela O
Kalkkinen N
Alitalo K
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1996-01-15
Pages
290-98
Language
English
Region
England
NLM ID
8208664
PMCID
PMC449944
Subset
IM
Databases
GENBANK
X94216
Corrections
ErratumIn
PMID: 8612600
External Links
PubMed source PMC Full Text View journal details
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