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Characterization of the Extracellular Domain in Vascular Endothelial Growth Factor Receptor‐1 (Flt‐1 Tyrosine Kinase)

Flt‐1 tyrosine kinase, vascular endothelial growth factor (VEGF) receptor‐1, binds VEGF and a new VEGF‐related ligand, placenta growth factor, but KDR/Flk‐1 (VEGF receptor‐2) binds only VEGF. To characterize the functional regions in the Flt‐1 extracellular domain such as the ligand binding region a...

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Detalles Bibliográficos
Autores principales: Tanaka, Keiji, Yamaguchi, Sachiko, Sawano, Asako, Shibuya, Masabumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 1997
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5921513/
https://www.ncbi.nlm.nih.gov/pubmed/9369935
http://dx.doi.org/10.1111/j.1349-7006.1997.tb00463.x
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author Tanaka, Keiji
Yamaguchi, Sachiko
Sawano, Asako
Shibuya, Masabumi
author_facet Tanaka, Keiji
Yamaguchi, Sachiko
Sawano, Asako
Shibuya, Masabumi
author_sort Tanaka, Keiji
collection PubMed
description Flt‐1 tyrosine kinase, vascular endothelial growth factor (VEGF) receptor‐1, binds VEGF and a new VEGF‐related ligand, placenta growth factor, but KDR/Flk‐1 (VEGF receptor‐2) binds only VEGF. To characterize the functional regions in the Flt‐1 extracellular domain such as the ligand binding region and the dimer formation of the receptor, we constructed a series of mutants of the Flt‐1 extracellular domain as soluble forms in a baculovirus system. We found that a region carrying the N‐terminal 1st to 3rd immunoglobulin (Ig)‐like domains of Flt‐1 binds both ligands with high affinity. However, for dimer formation of soluble Flt‐1, a region further downstream in the Flt‐1 extracellular domain was required. Mutant Flt‐1 receptors expressed in COS cells confirmed the requirement of the 4th to 7th Ig region for the activation of Flt‐1 tyrosine kinase. Soluble Flt‐1 carrying the N‐terminal 1st to 3rd Ig region suppressed VEGF‐dependent endothelial proliferation in vitro to the same level as the larger forms of soluble Flt‐1, suggesting that the binding of one soluble Flt‐1 molecule to one subunit of the VEGF homodimer may be sufficient to block the VEGF activity.
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spelling pubmed-59215132018-05-11 Characterization of the Extracellular Domain in Vascular Endothelial Growth Factor Receptor‐1 (Flt‐1 Tyrosine Kinase) Tanaka, Keiji Yamaguchi, Sachiko Sawano, Asako Shibuya, Masabumi Jpn J Cancer Res Article Flt‐1 tyrosine kinase, vascular endothelial growth factor (VEGF) receptor‐1, binds VEGF and a new VEGF‐related ligand, placenta growth factor, but KDR/Flk‐1 (VEGF receptor‐2) binds only VEGF. To characterize the functional regions in the Flt‐1 extracellular domain such as the ligand binding region and the dimer formation of the receptor, we constructed a series of mutants of the Flt‐1 extracellular domain as soluble forms in a baculovirus system. We found that a region carrying the N‐terminal 1st to 3rd immunoglobulin (Ig)‐like domains of Flt‐1 binds both ligands with high affinity. However, for dimer formation of soluble Flt‐1, a region further downstream in the Flt‐1 extracellular domain was required. Mutant Flt‐1 receptors expressed in COS cells confirmed the requirement of the 4th to 7th Ig region for the activation of Flt‐1 tyrosine kinase. Soluble Flt‐1 carrying the N‐terminal 1st to 3rd Ig region suppressed VEGF‐dependent endothelial proliferation in vitro to the same level as the larger forms of soluble Flt‐1, suggesting that the binding of one soluble Flt‐1 molecule to one subunit of the VEGF homodimer may be sufficient to block the VEGF activity. Blackwell Publishing Ltd 1997-09 /pmc/articles/PMC5921513/ /pubmed/9369935 http://dx.doi.org/10.1111/j.1349-7006.1997.tb00463.x Text en
spellingShingle Article
Tanaka, Keiji
Yamaguchi, Sachiko
Sawano, Asako
Shibuya, Masabumi
Characterization of the Extracellular Domain in Vascular Endothelial Growth Factor Receptor‐1 (Flt‐1 Tyrosine Kinase)
title Characterization of the Extracellular Domain in Vascular Endothelial Growth Factor Receptor‐1 (Flt‐1 Tyrosine Kinase)
title_full Characterization of the Extracellular Domain in Vascular Endothelial Growth Factor Receptor‐1 (Flt‐1 Tyrosine Kinase)
title_fullStr Characterization of the Extracellular Domain in Vascular Endothelial Growth Factor Receptor‐1 (Flt‐1 Tyrosine Kinase)
title_full_unstemmed Characterization of the Extracellular Domain in Vascular Endothelial Growth Factor Receptor‐1 (Flt‐1 Tyrosine Kinase)
title_short Characterization of the Extracellular Domain in Vascular Endothelial Growth Factor Receptor‐1 (Flt‐1 Tyrosine Kinase)
title_sort characterization of the extracellular domain in vascular endothelial growth factor receptor‐1 (flt‐1 tyrosine kinase)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5921513/
https://www.ncbi.nlm.nih.gov/pubmed/9369935
http://dx.doi.org/10.1111/j.1349-7006.1997.tb00463.x
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