The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
Angiopoietin-1 Regulates Endothelial Cell Survival Through the Phosphatidylinositol 3′-Kinase/Akt Signal Transduction Pathway
Open accessAbstract
Abstract —Angiopoietin-1 (Ang1) is a strong apoptosis survival factor for endothelial cells. In this study, the receptor/second messenger signal transduction pathway for the antiapoptotic effect of Ang1 on human umbilical vein endothelial cells was examined. Pretreatment with soluble Tie2 receptor, but not Tie1 receptor, blocked the Ang1-induced antiapoptotic effect. Ang1 induced phosphorylation of Tie2 and the p85 subunit of phosphatidylinositol 3′-kinase (PI 3′-kinase) and increased PI 3′-kinase activity in a dose-dependent manner. The PI 3′-kinase–specific inhibitors wortmannin and LY294002 blocked the Ang1-induced antiapoptotic effect. Ang1 induced phosphorylation of the serine-threonine kinase Akt at Ser473 in a PI 3′-kinase–dependent manner. Expression of a dominant-negative form of Akt reversed the Ang1-induced antiapoptotic effect. Ang1 mRNA and protein were present in vascular smooth muscle cells but not in endothelial cells. Cultured vascular smooth muscle cells, but not human umbilical vein endothelial cells, secreted Ang1. These findings indicate that the Tie2 receptor, PI 3′-kinase, and Akt are crucial elements in the signal transduction pathway leading to endothelial cell survival induced by the paracrine activity of Ang1.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“muscle secretes vascular endothelial growth factor (VEGF)45,46, angiopoietin 1 (REF.47) and IL-8 (REF.48) to regulate tissue angiogenesis, modulate blood flow and increase nutrient availability to support tissue growth27,49–52”
From Exerkines in health, resilience and disease (2022) · cites this paper as [47]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Apoptosis: A Basic Biological Phenomenon with Wideranging Implications in Tissue Kinetics
Kerr, J. F. R., Wyllie, A. H., & Currie, A. R. (1972) · British Journal of Cancer · doi:10.1038/bjc.1972.33 · Cited by 15,673
Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery
Datta, S. R., Dudek, H., Tao, X., Masters, S., Fu, H., Gotoh, Y., & Greenberg, M. E. (1997) · Cell · doi:10.1016/s0092-8674(00)80405-5 · Cited by 5,689
Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation
Dimmeler, S., Fleming, I., Fisslthaler, B., Hermann, C., Busse, R., & Zeiher, A. M. (1999) · Nature · doi:10.1038/21224 · Cited by 3,591
Angiopoietin-2, a Natural Antagonist for Tie2 That Disrupts in vivo Angiogenesis
Maisonpierre, P. C., Suri, C., Jones, P. F., Bartunkova, S., Wiegand, S. J., Radziejewski, C., Compton, D., McClain, J., Aldrich, T. H., Papadopoulos, N., et al. (1997) · Science · doi:10.1126/science.277.5322.55 · Cited by 3,570
Requisite Role of Angiopoietin-1, a Ligand for the TIE2 Receptor, during Embryonic Angiogenesis
Suri, C., Jones, P. F., Patan, S., Bartunkova, S., Maisonpierre, P. C., Davis, S. H., Sato, T. N., & Yancopoulos, G. D. (1996) · Cell · doi:10.1016/s0092-8674(00)81813-9 · Cited by 2,872
Regulation of endothelium-derived nitric oxide production by the protein kinase Akt
Fulton, D. J., Gratton, J., McCabe, T. J. D., Fontana, J. T., Fujio, Y., Walsh, K. X., Franke, T. F., Papapetropoulos, A., & Sessa, W. C. (1999) · Nature · doi:10.1038/21218 · Cited by 2,585
Regulation of Cell Death Protease Caspase-9 by Phosphorylation
Cardone, M. H., Roy, N., Stennicke, H. R., Salvesen, G. S., Franke, T. F., Stanbridge, E., Frisch, S., & Reed, J. C. (1998) · Science · doi:10.1126/science.282.5392.1318 · Cited by 2,481
Vessel Cooption, Regression, and Growth in Tumors Mediated by Angiopoietins and VEGF
Holash, J. A., Maisonpierre, P. C., Compton, D. L., Boland, P., Alexander, C., Zagzag, D., Yancopoulos, G. D., & Wiegand, S. J. (1999) · Science · doi:10.1126/science.284.5422.1994 · Cited by 2,222
Gerber, H. P., McMurtrey, A. E., Kowalski, J., Yan, M., Keyt, B. A., Dixit, V. M., & Ferrara, N. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.46.30336 · Cited by 2,007
Isolation of Angiopoietin-1, a Ligand for the TIE2 Receptor, by Secretion-Trap Expression Cloning
Davis, S., Aldrich, T. H., Jones, P. F., Acheson, A., Compton, D. L., Jain, V., Ryan, T. E., Bruno, J., Radziejewski, C., Maisonpierre, P. C., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)81812-7 · Cited by 1,989
Cytokines and endothelial cell biology
Pober, J. S., & Cotran, R. S. (1990) · Physiological Reviews · doi:10.1152/physrev.1990.70.2.427 · Cited by 1,251
Gerber, H., Dixit, V. M., & Ferrara, N. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.21.13313 · Cited by 991
A Retroviral Oncogene, akt , Encoding a Serine-Threonine Kinase Containing an SH2-Like Region
Bellacosa, A., Testa, J. R., Staal, S. P., & Tsichlis, P. N. (1991) · Science · doi:10.1126/science.1833819 · Cited by 939
Increased Vascularization in Mice Overexpressing Angiopoietin-1
Suri, C., McClain, J., Thurston, G., McDonald, D. M., Zhou, H., Oldmixon, E. H., Sato, T. N., & Yancopoulos, G. D. (1998) · Science · doi:10.1126/science.282.5388.468 · Cited by 818
Haunstetter, A., & Izumo, S. (1998) · Circulation Research · doi:10.1161/01.res.82.11.1111 · Cited by 802
Cytokine regulation of endothelial cell function
Mantovani, A., Bussolino, F., & Dejana, E. (1992) · The FASEB Journal · doi:10.1096/fasebj.6.8.1592209 · Cited by 677
A rapid and simple method for the isolation of apoptotic DNA fragments
i, M. H., Lorenz, H.-M., Voll, R. E., Griinke, M., Woith, W., & Kalden, J. R. (1994) · Nucleic Acids Research · doi:10.1093/nar/22.24.5506 · Cited by 652
Sato, T. N., Qin, Y., Kozak, C. A., & Audus, K. L. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.20.9355 · Cited by 462
Angiopoietin-1 induces sprouting angiogenesis in vitro
Koblizek, T. I., Weiss, C., Yancopoulos, G. D., Deutsch, U., & Risau, W. (1998) · Current Biology · doi:10.1016/s0960-9822(98)70205-2 · Cited by 459
Witzenbichler, B., Maisonpierre, P. C., Jones, P. F., Yancopoulos, G. D., & Isner, J. M. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.29.18514 · Cited by 433
Papapetropoulos, A., García‐Cardeña, G., Dengler, T. J., Maisonpierre, P. C., Yancopoulos, G. D., & Sessa, W. C. (1999) · PubMed · Cited by 418
Interleukin 3-dependent survival by the Akt protein kinase
Songyang, Z., Baltimore, D., Cantley, L. C., Kaplan, D. R., & Franke, T. F. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.21.11345 · Cited by 361
Angiopoietin‐1 is an apoptosis survival factor for endothelial cells
Kwak, H. J., So, J.-N., Lee, S. J., Kim, I., & Koh, G. Y. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)00378-6 · Cited by 238
Self-citationKontos, C. D., Stauffer, T. P., Yang, W.-P., York, J. D., Huang, L., Blanar, M. A., Meyer, T., & Peters, K. G. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.7.4131 · Cited by 226
Molecular Cloning, Expression, and Characterization of Angiopoietin-related Protein
Kim, I., Moon, S.-O., Koh, K. N., Kim, H., Uhm, C.-S., Kwak, H. J., Kim, N.-G., & Koh, G. Y. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.37.26523 · Cited by 212
Self-citationShyu, K., Manor, O., Magner, M., Yancopoulos, G. D., & Isner, J. M. (1998) · Circulation · doi:10.1161/01.cir.98.19.2081 · Cited by 188
Endothelin-1 as an Autocrine/Paracrine Apoptosis Survival Factor for Endothelial Cells
Shichiri, M., Kato, H., Marumo, F., & Hirata, Y. (1997) · Hypertension · doi:10.1161/01.hyp.30.5.1198 · Cited by 176
The Tek/Tie2 receptor signals through a novel Dok-related docking protein, Dok-R
Jones, N., & Dumont, D. (1998) · Oncogene · doi:10.1038/sj.onc.1202115 · Cited by 150
Araki, S., Simada, Y., Kaji, K., & Hayashi, H. (1990) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(90)91557-9 · Cited by 116
Adrenergic Receptors Activate Phosphatidylinositol 3-Kinase in Human Vascular Smooth Muscle Cells
Hu, Z., Shi, X., Lin, R. Z., & Hoffman, B. B. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.15.8977 · Cited by 115
Downward, J. (1995) · Nature · doi:10.1038/376553a0 · Cited by 80
The Endothelium : an introduction to current research
Warren, J. B. (1990) · Wiley-Liss eBooks · Cited by 62
Koh, K. N., Kang, M. J., Frith, A., Park, S. K., Kim, I., Lee, C. O., & Koh, G. Y. (1998) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.1997.0611 · Cited by 48
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Tie2/Angiopoietin-1 Signaling Regulates Hematopoietic Stem Cell Quiescence in the Bone Marrow Niche
Arai, F., Hirao, A., Ohmura, M., Sato, H., Matsuoka, S., Takubo, K., Ito, K., Koh, G. Y., & Suda, T. (2004) · Cell · doi:10.1016/j.cell.2004.07.004 · Cited by 1,958
Self-citationThe protein kinase B/Akt signalling pathway in human malignancy
Nicholson, K. M., & Anderson, N. G. (2002) · Cellular Signalling · doi:10.1016/s0898-6568(01)00271-6 · Cited by 1,665
PI3K/AKT/mTOR Pathway in Angiogenesis
Karar, J., & Maity, A. (2011) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2011.00051 · Cited by 1,493
Control of vascular morphogenesis and homeostasis through the angiopoietin–Tie system
Augustin, H. G., Koh, G. Y., Thurston, G., & Alitalo, K. K. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2639 · Cited by 1,512
Self-citationKureishi, Y., Luo, Z., Shiojima, I., Bialik, A., Fulton, D. J., Lefer, D. J., Sessa, W. C., & Walsh, K. X. (2000) · Nature Medicine · doi:10.1038/79510 · Cited by 1,438
Metadata
- Authors
- Kim, I., Kim, H. G., So, J.-N., Kim, J. H., Kwak, H. J., & Koh, G. Y.
- Affiliations
- Woosuk University (KR)
- Venue
- Circulation Research
- Published
- 2000-01-07
- Volume
- 86
- Issue
- 1
- Pages
- 24-29
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2167839699
- Cited by
- 649
- References
- 33
- Citations by year
- 2026: 14 · 2025: 16 · 2024: 18 · 2023: 26 · 2022: 17 · 2021: 25 · 2020: 17 · 2019: 16 · 2018: 18 · 2017: 16 · 2016: 30 · 2015: 17 · 2014: 23 · 2013: 26 · 2012: 25
- FWCI
- 11.21
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Centre International de Recherche sur le Cancer
- Regeneron Pharmaceuticals
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Oncology › Vascular Tumors and Angiosarcomas
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- angiopoietin-1, endothelial cell survival, apoptosis, Tie2 receptor, phosphatidylinositol 3-kinase, Akt signaling, PI3K/Akt signaling, vascular smooth muscle cells, paracrine secretion, wortmannin, LY294002, dominant-negative Akt, human umbilical vein endothelial cells
- MeSH terms
- Cell Survival, Cells, Cultured, Endothelium, Vascular, Humans, Membrane Glycoproteins, Neoplasm Proteins, Peptide Fragments, Phosphorylation, Proto-Oncogene Proteins, Recombinant Proteins, Signal Transduction, Apoptosis, Protein Serine-Threonine Kinases, Phosphatidylinositol 3-Kinases, Paracrine Communication, Angiopoietin-1, Receptor, TIE-2, Proto-Oncogene Proteins c-akt
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
