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- Title
Characterization of murine Flt4 ligand/VEGF-C.
- Authors
Fitz, L J; Morris, J C; Towler, P; Long, A; Burgess, P; Greco, R; Wang, J; Gassaway, R; Nickbarg, E; Kovacic, S; Ciarletta, A; Giannotti, J; Finnerty, H; Zollner, R; Beier, D R; Leak, L V; Turner, K J; Wood, C R
- Abstract
Flt4 is a receptor protein tyrosine kinase that is expressed in the adult lymphatic endothelium and high endothelial venules. We have used a BIAcore assay to identify rodent and human cell conditioned media containing the ligand of Flt4 (Flt4-L). Receptor-based affinity chromatography was used to purify this growth factor, followed by amino acid sequencing and molecular cloning of the murine cDNA, the orthologue of human vascular endothelial growth factor-C and vascular endothelial growth factor related protein. The murine flt4-L gene was localized to chromosome 8 and demonstrated to be widely expressed. Flt4-L was found to have a hydrophobic signal sequence and a pro-peptide-like sequence that is removed to generate the mature N-terminus. In addition, the C-terminal region of Flt4-L has four repeats of a cysteine-rich motif that is presumably also proteolytically processed to generate the 21000 Mr polypeptide subunit of the Flt4-L homodimer. Recombinant Flt4-L activated Flt4 as judged by induction of tyrosyl phosphorylation, and induced mitogenesis in vitro of lymphatic endothelial cells.
- Publication
Oncogene, 1997, Vol 15, Issue 5, p613
- ISSN
0950-9232
- Publication type
Journal Article
- DOI
10.1038/sj.onc.1201191