The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
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
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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“By ineffectively occupying a binding site on the receptor, the VEGFXXXb isoforms inhibit the function of the VEGFXXX variants [36, 200].”
From Intrinsically disordered proteins play diverse roles in cell signaling (2022) · cites this paper as [36]
In the citing paper
“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].”
From Intrinsically disordered proteins play diverse roles in cell signaling (2022) · cites this paper as [36]
Citations
Cites
Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele
Carmeliet, P., Ferreira, V., Breier, G., Pollefeyt, S., Kieckens, L., Gertsenstein, M., Fahrig, M., Vandenhoeck, A., Harpal, K., Eberhardt, C., et al. (1996) · Nature · doi:10.1038/380435a0 · Cited by 4,162
Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice
Shalaby, F., Rossant, J., Yamaguchi, T. P., Gertsenstein, M., Wu, X.-F., Breitman, M. L., & Schuh, A. C. (1995) · Nature · doi:10.1038/376062a0 · Cited by 3,931
Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene
Ferrara, N., Carver-Moore, K., Chen, H., Dowd, M., Lu, L., O’Shea, K. S., Powell-Braxton, L., Hillan, K. J., & Moore, M. W. (1996) · Nature · doi:10.1038/380439a0 · Cited by 3,661
VEGF receptor signalling ? in control of vascular function
Olsson, A.-K., Dimberg, A., Kreuger, J., & Claesson-Welsh, L. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1911 · Cited by 3,122
Söker, S., Takashima, S., Miao, H. Q., Neufeld, G., & Klagsbrun, M. (1998) · Cell · doi:10.1016/s0092-8674(00)81402-6 · Cited by 2,493
Waltenberger, J. L., Claesson, L., Siegbahn, A., Shibuya, M., & Heldin, C. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47116-5 · Cited by 1,661
Order Out of Chaos: Assembly of Ligand Binding Sites in Heparan Sulfate
Esko, J. D., & Selleck, S. B. (2002) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.71.110601.135458 · Cited by 1,495
Neuropilin is a semaphorin III receptor.
Kolodkin, A., Levengood, D. V., Rowe, E. G., Tai, Y.-T., Giger, R., & Ginty, D. (1997) · Cell · doi:10.1016/s0092-8674(00)80535-8 · Cited by 1,262
Neuropilin Is a Receptor for the Axonal Chemorepellent Semaphorin III
He, Z., & Tessier‐Lavigne, M. (1997) · Cell · doi:10.1016/s0092-8674(00)80534-6 · Cited by 1,137
VEGF-receptor signal transduction
Cross, M. J., Dixelius, J., Matsumoto, T., & Claesson, L. (2003) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(03)00193-2 · Cited by 890
A requirement for neuropilin-1 in embryonic vessel formation
Kawasaki, T., Kitsukawa, T., Bekku, Y., Matsuda, Y., Sanbo, M., Yagi, T., & Fujisawa, H. (1999) · Development · doi:10.1242/dev.126.21.4895 · Cited by 844
(2002) · PubMed · Cited by 550
Self-citationVEGF145, a Secreted Vascular Endothelial Growth Factor Isoform That Binds to Extracellular Matrix
Gluzman‐Poltorak, Z., Cohen, T., Sivan, R., Kandelis, Y., Spira, G., Vlodavsky, I., Keshet, E., & Neufeld, G. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.11.7151 · Cited by 519
Muller, Y. A., Li, B., Christinger, H. W., Wells, J. A., Cunningham, B. C., & de Vos, A. M. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.14.7192 · Cited by 467
VEGF165b, an Inhibitory Vascular Endothelial Growth Factor Splice Variant
Woolard, J., Wang, W.-Y., Bevan, H. S., Qiu, Y., Morbidelli, L., Pritchard-Jones, R. O., Cui, T.-G., Sugiono, M., Waine, E., Perrin, R., et al. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-0934 · Cited by 451
Self-citationThe Mouse Gene for Vascular Endothelial Growth Factor
Shima, D. T., Kuroki, M., Deutsch, U., Ng, Y., Adamis, A. P., & D'Amore, P. A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.7.3877 · Cited by 332
The role of VEGF in the regulation of physiological and pathological angiogenesis
Ferrara, N. (2005) · Birkhäuser Basel eBooks · doi:10.1007/3-7643-7311-3_15 · Cited by 322
VEGF receptor‐2 Y951 signaling and a role for the adapter molecule TSAd in tumor angiogenesis
Matsumoto, T., Bohman, S., Dixelius, J., Berge, T., Dimberg, A., Magnusson, P. U., Ling, W., Wikner, C., Qi, J. H., Wernstedt, C., et al. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600709 · Cited by 292
Dixelius, J., Mäkinen, T., Wirzenius, M., Karkkainen, M. J., Wernstedt, C., Alitalo, K. K., & Claesson, L. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304499200 · Cited by 285
Heparan Sulfate in trans Potentiates VEGFR-Mediated Angiogenesis
Jakobsson, L., Kreuger, J., Holmborn, K., Lundin, L., Eriksson, I., Kjellén, L., & Claesson, L. (2006) · Developmental Cell · doi:10.1016/j.devcel.2006.03.009 · Cited by 282
Varey, A. H. R., Rennel, E. S., Qiu, Y., Bevan, H. S., Perrin, R. M., Raffy, S., Dixon, A., Paraskeva, C., Zaccheo, O., Hassan, A. B., et al. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604308 · Cited by 231
Self-citationSuarez, S., Pieren, M., Cariolato, L., Arn, S., Hoffmann, U., Bogucki, A., Manlius, C., Wood, J. M., & Ballmer‐Hofer, K. (2006) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-006-6254-9 · Cited by 208
Landgren, E., Schiller, P., Cao, Y., & Claesson, L. (1998) · Oncogene · doi:10.1038/sj.onc.1201545 · Cited by 167
Jia, H., Bagherzadeh, A., Hartzoulakis, B., Jarvis, A., Löhr, M., Shaikh, S., Aqil, R., Cheng, L., Tickner, M. L., Esposito, D., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m512121200 · Cited by 138
The endogenous anti-angiogenic VEGF isoform, VEGF165b inhibits human tumour growth in mice
Rennel, E. S., Waine, E., Guan, H., Schüler, Y., Leenders, W. P. J., Woolard, J., Sugiono, M., Gillatt, D. A., Kleinerman, E. S., Bates, D. O., et al. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604309 · Cited by 131
Self-citationIto, N., Wernstedt, C., Engström, U., & Claesson, L. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.36.23410 · Cited by 118
Identification of a Heparin Binding Peptide on the Extracellular Domain of the KDR VEGF Receptor
Dougher, A. M., Wasserstrom, H. A., Torley, L. W., Shridaran, L., Westdock, P., Hileman, R. E., Fromm, J. R., Anderberg, R. J., Lyman, S. D., Linhardt, R. J., et al. (1997) · Growth Factors · doi:10.3109/08977199709021524 · Cited by 95
Building blood vessels—stem cell models in vascular biology
Jakobsson, L., Kreuger, J., & Claesson, L. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200701146 · Cited by 93
Self-citationRecombinant human VEGF165b protein is an effective anti-cancer agent in mice
Rennel, E., Hamdollah‐Zadeh, M., Wheatley, E. R., Magnussen, A., Schüler, Y., Kelly, S., Finucane, C. M., Ellison, D. H., Suarez, S., Ballmer‐Hofer, K., et al. (2008) · European Journal of Cancer · doi:10.1016/j.ejca.2008.05.027 · Cited by 80
Self-citationNitrocellulose Filter Binding to Assess Binding of Glycosaminoglycans to Proteins
Kreuger, J., Lindahl, U., & Jemth, P. (2003) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(03)01062-0 · Cited by 28
Li, X., Edholm, D., Lanner, F., Breier, G., Farnebo, F. A., Dimberg, A., & Claesson, L. (2007) · Stem Cells · doi:10.1634/stemcells.2007-0397 · Cited by 16
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Simons, M., Gordon, E., & Claesson-Welsh, L. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.87 · Cited by 1,498
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Metadata
- 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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