The fourth immunoglobulin-like loop in the extracellular domain of FLT-1, a VEGF receptor, includes a major heparin-binding site

Mikyoung Park, Seung-Taek Lee

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45 Citations (Scopus)

Abstract

We found that heparin at low concentrations increases the vascular endothelial growth factor (VEGF)-induced proliferation of human umbilical vein endothelial cells (HUVECs) but at high concentrations decreases it. To examine whether FLT-1, a VEGF receptor, interacts with heparin and which domain of FLT-1 binds to heparin, various extracellular domains of FLT-1 were expressed in a baculovirus/insect cell system: sFLT-1(1-7), sFLT-1(1-4), sFLT-1(1-3), and sFLT-1(1-2) containing immunoglobulin (Ig)-like loop one to seven, one to four, one to three, and one to two, respectively. The sFLT-1(1-7) and sFLT-1(1-4) readily bound heparin at the physiological salt concentration and half-dissociated from heparin at 0.65 M and 0.57 M NaCl, respectively. In contrast, the sFLT-1(1-3) and sFLT-1(1-2) poorly bound heparin at the physiological salt concentration. In addition, the interaction of sFLT-1(1-7) with heparin was not affected by EDTA up to 80 mM. We thus concluded that the fourth Ig-like loop of FLT-1 is a major heparin-binding site and divalent cations are not involved in the interaction of FLT-1 and heparin.

Original languageEnglish
Pages (from-to)730-734
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume264
Issue number3
DOIs
Publication statusPublished - 1999 Nov 2

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Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factor Receptor
Heparin
Immunoglobulins
Binding Sites
Salts
Baculoviridae
Endothelial cells
Divalent Cations
Human Umbilical Vein Endothelial Cells
Edetic Acid
Vascular Endothelial Growth Factor A
Insects

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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abstract = "We found that heparin at low concentrations increases the vascular endothelial growth factor (VEGF)-induced proliferation of human umbilical vein endothelial cells (HUVECs) but at high concentrations decreases it. To examine whether FLT-1, a VEGF receptor, interacts with heparin and which domain of FLT-1 binds to heparin, various extracellular domains of FLT-1 were expressed in a baculovirus/insect cell system: sFLT-1(1-7), sFLT-1(1-4), sFLT-1(1-3), and sFLT-1(1-2) containing immunoglobulin (Ig)-like loop one to seven, one to four, one to three, and one to two, respectively. The sFLT-1(1-7) and sFLT-1(1-4) readily bound heparin at the physiological salt concentration and half-dissociated from heparin at 0.65 M and 0.57 M NaCl, respectively. In contrast, the sFLT-1(1-3) and sFLT-1(1-2) poorly bound heparin at the physiological salt concentration. In addition, the interaction of sFLT-1(1-7) with heparin was not affected by EDTA up to 80 mM. We thus concluded that the fourth Ig-like loop of FLT-1 is a major heparin-binding site and divalent cations are not involved in the interaction of FLT-1 and heparin.",
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AU - Lee, Seung-Taek

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N2 - We found that heparin at low concentrations increases the vascular endothelial growth factor (VEGF)-induced proliferation of human umbilical vein endothelial cells (HUVECs) but at high concentrations decreases it. To examine whether FLT-1, a VEGF receptor, interacts with heparin and which domain of FLT-1 binds to heparin, various extracellular domains of FLT-1 were expressed in a baculovirus/insect cell system: sFLT-1(1-7), sFLT-1(1-4), sFLT-1(1-3), and sFLT-1(1-2) containing immunoglobulin (Ig)-like loop one to seven, one to four, one to three, and one to two, respectively. The sFLT-1(1-7) and sFLT-1(1-4) readily bound heparin at the physiological salt concentration and half-dissociated from heparin at 0.65 M and 0.57 M NaCl, respectively. In contrast, the sFLT-1(1-3) and sFLT-1(1-2) poorly bound heparin at the physiological salt concentration. In addition, the interaction of sFLT-1(1-7) with heparin was not affected by EDTA up to 80 mM. We thus concluded that the fourth Ig-like loop of FLT-1 is a major heparin-binding site and divalent cations are not involved in the interaction of FLT-1 and heparin.

AB - We found that heparin at low concentrations increases the vascular endothelial growth factor (VEGF)-induced proliferation of human umbilical vein endothelial cells (HUVECs) but at high concentrations decreases it. To examine whether FLT-1, a VEGF receptor, interacts with heparin and which domain of FLT-1 binds to heparin, various extracellular domains of FLT-1 were expressed in a baculovirus/insect cell system: sFLT-1(1-7), sFLT-1(1-4), sFLT-1(1-3), and sFLT-1(1-2) containing immunoglobulin (Ig)-like loop one to seven, one to four, one to three, and one to two, respectively. The sFLT-1(1-7) and sFLT-1(1-4) readily bound heparin at the physiological salt concentration and half-dissociated from heparin at 0.65 M and 0.57 M NaCl, respectively. In contrast, the sFLT-1(1-3) and sFLT-1(1-2) poorly bound heparin at the physiological salt concentration. In addition, the interaction of sFLT-1(1-7) with heparin was not affected by EDTA up to 80 mM. We thus concluded that the fourth Ig-like loop of FLT-1 is a major heparin-binding site and divalent cations are not involved in the interaction of FLT-1 and heparin.

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