PMID- 10542248
OWN - NLM
STAT- MEDLINE
DCOM- 19991213
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 45
DP  - 1999 Nov 5
TI  - Biosynthesis of vascular endothelial growth factor-D involves proteolytic
      processing which generates non-covalent homodimers.
PG  - 32127-36
AB  - 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 N-
      and C-terminal cleavage events to produce numerous secreted polypeptides
      including a fully processed form of M(r) approximately 21,000 consisting only of 
      the VHD, which is predominantly a non-covalent dimer. Biosensor analysis
      demonstrated that the VHD has approximately 290- and approximately 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.
FAU - Stacker, S A
AU  - Stacker SA
AD  - Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Parkville,
      Victoria 3050, Australia. steven.stacker@ludwig.edu.au
FAU - Stenvers, K
AU  - Stenvers K
FAU - Caesar, C
AU  - Caesar C
FAU - Vitali, A
AU  - Vitali A
FAU - Domagala, T
AU  - Domagala T
FAU - Nice, E
AU  - Nice E
FAU - Roufail, S
AU  - Roufail S
FAU - Simpson, R J
AU  - Simpson RJ
FAU - Moritz, R
AU  - Moritz R
FAU - Karpanen, T
AU  - Karpanen T
FAU - Alitalo, K
AU  - Alitalo K
FAU - Achen, M G
AU  - Achen MG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Endothelial Growth Factors)
RN  - 0 (Indicators and Reagents)
RN  - 0 (Oligopeptides)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, Growth Factor)
RN  - 0 (Receptors, Mitogen)
RN  - 0 (Vascular Endothelial Growth Factor D)
RN  - 98849-88-8 (FLAG peptide)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-3)
SB  - IM
MH  - Cell Division
MH  - Cell Line
MH  - Dimerization
MH  - Endothelial Growth Factors/*biosynthesis
MH  - Endothelium, Vascular/metabolism
MH  - Humans
MH  - In Situ Hybridization
MH  - Indicators and Reagents
MH  - Oligopeptides
MH  - Peptides
MH  - Protein Processing, Post-Translational
MH  - Receptor Protein-Tyrosine Kinases/metabolism
MH  - Receptors, Cell Surface/metabolism
MH  - Receptors, Growth Factor/metabolism
MH  - Receptors, Mitogen/metabolism
MH  - Receptors, Vascular Endothelial Growth Factor
MH  - Vascular Endothelial Growth Factor D
MH  - Vascular Endothelial Growth Factor Receptor-3
EDAT- 1999/11/05 00:00
MHDA- 1999/11/05 00:01
CRDT- 1999/11/05 00:00
PHST- 1999/11/05 00:00 [pubmed]
PHST- 1999/11/05 00:01 [medline]
PHST- 1999/11/05 00:00 [entrez]
AID - 10.1074/jbc.274.45.32127 [doi]
AID - S0021-9258(19)51536-8 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Nov 5;274(45):32127-36. doi: 10.1074/jbc.274.45.32127.