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PMID:9012504

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Citation

Kukk, E, Lymboussaki, A, Taira, S, Kaipainen, A, Jeltsch, M, Joukov, V and Alitalo, K (1996) VEGF-C receptor binding and pattern of expression with VEGFR-3 suggests a role in lymphatic vascular development. Development 122:3829-37

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.

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PubMed

Keywords

Amino Acid Sequence; Animals; Cloning, Molecular; Endothelial Growth Factors/genetics; Endothelial Growth Factors/metabolism; In Situ Hybridization; Ligands; Lymphatic System/embryology; Mice; Molecular Sequence Data; Phosphorylation; Protein Binding; RNA, Messenger/analysis; Receptor Protein-Tyrosine Kinases/metabolism; Receptors, Cell Surface/metabolism; Receptors, Growth Factor/metabolism; Receptors, Vascular Endothelial Growth Factor; Recombinant Proteins/secretion; Sequence Analysis, DNA; Sequence Homology, Amino Acid; Tissue Distribution; Vascular Endothelial Growth Factor C; Vascular Endothelial Growth Factor Receptor-3

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


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