PMID- 10196157
OWN - NLM
STAT- MEDLINE
DCOM- 19990517
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 16
DP  - 1999 Apr 16
TI  - Glypican-1 is a VEGF165 binding proteoglycan that acts as an extracellular
      chaperone for VEGF165.
PG  - 10816-22
AB  - Glypican-1 is a member of a family of glycosylphosphatidylinositol anchored cell 
      surface heparan sulfate proteoglycans implicated in the control of cellular
      growth and differentiation. The 165-amino acid form of vascular endothelial
      growth factor (VEGF165) is a mitogen for endothelial cells and a potent
      angiogenic factor in vivo. Heparin binds to VEGF165 and enhances its binding to
      VEGF receptors. However, native HSPGs that bind VEGF165 and modulate its receptor
      binding have not been identified. Among the glypicans, glypican-1 is the only
      member that is expressed in the vascular system. We have therefore examined
      whether glypican-1 can interact with VEGF165. Glypican-1 from rat myoblasts binds
      specifically to VEGF165 but not to VEGF121. The binding has an apparent
      dissociation constant of 3 x 10(-10) M. The binding of glypican-1 to VEGF165 is
      mediated by the heparan sulfate chains of glypican-1, because heparinase
      treatment abolishes this interaction. Only an excess of heparin or heparan
      sulfates but not other types of glycosaminoglycans inhibited this interaction.
      VEGF165 interacts specifically not only with rat myoblast glypican-1 but also
      with human endothelial cell-derived glypican-1. The binding of 125I-VEGF165 to
      heparinase-treated human vascular endothelial cells is reduced following
      heparinase treatment, and addition of glypican-1 restores the binding. Glypican-1
      also potentiates the binding of 125I-VEGF165 to a soluble extracellular domain of
      the VEGF receptor KDR/flk-1. Furthermore, we show that glypican-1 acts as an
      extracellular chaperone that can restore the receptor binding ability of VEGF165,
      which has been damaged by oxidation. Taken together, these results suggest that
      glypican-1 may play an important role in the control of angiogenesis by
      regulating the activity of VEGF165, a regulation that may be critical under
      conditions such as wound repair, in which oxidizing agents that can impair the
      activity of VEGF are produced, and in situations were the concentrations of
      active VEGF are limiting.
FAU - Gengrinovitch, S
AU  - Gengrinovitch S
AD  - Department of Biology, Technion-Israel Institute of Technology, Haifa 32000,
      Israel.
FAU - Berman, B
AU  - Berman B
FAU - David, G
AU  - David G
FAU - Witte, L
AU  - Witte L
FAU - Neufeld, G
AU  - Neufeld G
FAU - Ron, D
AU  - Ron D
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 (Lymphokines)
RN  - 0 (Membrane Proteins)
RN  - 0 (Molecular Chaperones)
RN  - 0 (Proteoglycans)
RN  - 0 (Recombinant Proteins)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Vascular Endothelial Growth Factors)
SB  - IM
MH  - Endothelial Growth Factors/*metabolism
MH  - Humans
MH  - Lymphokines/*metabolism
MH  - Membrane Proteins/metabolism
MH  - Molecular Chaperones/*metabolism
MH  - Oxidation-Reduction
MH  - Protein Binding
MH  - Proteoglycans/*metabolism
MH  - Recombinant Proteins/metabolism
MH  - Vascular Endothelial Growth Factor A
MH  - Vascular Endothelial Growth Factors
EDAT- 1999/04/10 00:00
MHDA- 1999/04/10 00:01
CRDT- 1999/04/10 00:00
PHST- 1999/04/10 00:00 [pubmed]
PHST- 1999/04/10 00:01 [medline]
PHST- 1999/04/10 00:00 [entrez]
AID - 10.1074/jbc.274.16.10816 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Apr 16;274(16):10816-22. doi: 10.1074/jbc.274.16.10816.