Cited by 156Angiogenesis and VEGF in CancerLymphatic System and DiseasesAxon Guidance and Neuronal Signaling

Vascular Endothelial Growth Factor (VEGF)-A165b Is a Weak In vitro Agonist for VEGF Receptor-2 Due to Lack of Coreceptor Binding and Deficient Regulation of Kinase Activity

Kawamura, Harukiyo, Li, Xiujuan, Harper, Steven J., Bates, David O., Claesson-Welsh, Lena·2008·Cancer Research

Abstract

Vascular endothelial growth factor (VEGF)-A165b is a COOH-terminal splice variant of VEGF-A that has been implicated in negative regulation of angiogenesis. We compared the properties of VEGF-A165b with those of VEGF-A121, VEGF-A145, and VEGF-A165. Induction of tyrosine phosphorylation sites in VEGFR-2 differed between the VEGF ligands as determined by tryptic phosphopeptide mapping and by use of phosphosite-specific antibodies. VEGF-A165b was considerably poorer in inducing phosphorylation of the positive regulatory site Y1052 in VEGFR-2. Whereas this did not affect activation of VEGFR-2 in vitro, we show that VEGF-A165b failed to induce vasculogenesis and sprouting angiogenesis in differentiating embryonic stem cells and vascularization of s.c. Matrigel plugs. In addition, the ability of the different VEGF ligands to induce angiogenesis correlated with their abilities to bind the VEGF coreceptor neuropilin 1 (NRP1). Our data indicate that loss of VEGFR-2/NRP1 complex formation and Y1052 phosphorylation contribute to the lack of angiogenic properties of VEGF-A165b. [Cancer Res 2008;68(12):4683–92]

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Crossref · 10.1158/0008-5472.can-07-6577

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31 of 31 references verified0 citation errors · 0 not checkable

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  • VEGFXXXb isoforms inhibit the function of VEGFXXX variants by ineffectively occupying a binding site on the receptor.

    “By ineffectively occupying a binding site on the receptor, the VEGFXXXb isoforms inhibit the function of the VEGFXXX variants [36, 200].”
  • VEGF B splice variants are generated by use of an alternate 3' acceptor site for exon 8, lengthening the intrinsically disordered C-terminal tail by an additional 6 amino acids.

    “The VEGF “B” splice variants are generated by use of an alternate 3’ acceptor site for exon 8, lengthening the intrinsically disordered C-terminal tail by an additional 6 amino acids (e.g., VEGF165 versus VEGF165b) [36, 200].”

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Authors
Kawamura, H., Li, X., Harper, S. J., Bates, D. O., & Claesson-Welsh, L.
Affiliations
  • Uppsala University (SE)
  • University of Bristol (GB)
  • 1Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden; and
Venue
Cancer Research
Published
2008-06-15
Volume
68
Issue
12
Pages
4683-4692
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
OpenAlex
W2067020920
Cited by
156
References
31
Citations by year
2025: 4 · 2024: 3 · 2023: 5 · 2022: 8 · 2021: 6 · 2020: 4 · 2019: 10 · 2018: 13 · 2017: 11 · 2016: 10 · 2015: 11 · 2014: 14 · 2013: 9 · 2012: 11
FWCI
5.08
Type
journal article
Language
en
Open access
closed
Locations
  • Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
Keywords
VEGF-A165b, VEGF splice variants, VEGF receptor 2, neuropilin-1, tyrosine phosphorylation, kinase regulation, angiogenesis, vasculogenesis, sprouting angiogenesis, embryonic stem cells
MeSH terms
Animals, Aorta, Binding, Competitive, Cell Differentiation, Cells, Cultured, Chemotaxis, Collagen, Drug Combinations, Embryo, Mammalian, Endothelium, Vascular, Female, Gene Expression Regulation, Heparitin Sulfate, Heparan Sulfate, Humans, Laminin, Mice, Nude, Phosphorylation, Protein Binding, Proteoglycans, Swine, Tyrosine, Immunoblotting, Signal Transduction, Neovascularization, Physiologic, Neuropilin-1, Vascular Endothelial Growth Factor Receptor-2, Vascular Endothelial Growth Factor A, Immunoprecipitation, Mice

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