Biosynthesis of vascular endothelial growth factor-D involves proteolytic processing which generates non-covalent homodimers
- Author(s)
- Stacker, SA; Stenvers, K; Caesar, C; Vitali, A; Domagala, T; Nice, E; Roufail, S; Simpson, RJ; Moritz, R; Karpanen, T; Alitalo, K; Achen, MG;
- Details
- Publication Year 1999-11-05,Volume 274,Issue #45,Page 32127-32136
- Journal Title
- JOURNAL OF BIOLOGICAL CHEMISTRY
- Publication Type
- Journal Article
- Abstract
- Vascular endothelial growth factor-D (VEGF-D) binds and activates the endothelial cell tyrosine kinase receptors VEGF receptor-2 (VEGFR-2) and VEGF receptor-3 (VEGFR-3), is mitogenic for endothelial cells, and shares structural homology and receptor specificity with VEGF-C, The primary translation product of VEGF-D has long N- and C-terminal polypeptide extensions in addition to a central VEGF homology domain (VHD). The VHD of VEGF-D is sufficient to bind and activate VEGFR-2 and VEGFR-3. Here we report that VEGF-D is proteolytically processed to release the VHD. Studies in 293EBNA cells demonstrated that VEGF-D undergoes Nand C-terminal cleavage events to produce numerous secreted polypeptides including a fully processed form of M-r similar to 21,000 consisting only of the VHD, which is predominantly a non-covalent dimer. Biosensor analysis demonstrated that the VHD has similar to 290- and similar to 40-fold greater affinity for VEGFR-2 and VEGFR-3, respectively, compared with unprocessed VEGF-D. In situ hybridization demonstrated that embryonic lung is a major site of expression of the VEGF-D gene. Processed forms of VEGF-D were detected in embryonic lung indicating that VEGF-D is proteolytically processed in vivo.
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- Keywords
- INTERCHAIN DISULFIDE BONDS; VEGF-C; CRYSTAL-STRUCTURE; TYROSINE KINASES; FACTOR FAMILY; IN-VIVO; RECEPTOR; ANGIOGENESIS; BINDING; EXPRESSION
- Publisher's Version
- https://doi.org/10.1074/jbc.274.45.32127
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 1999-11-05 12:00:00