The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Phosphorylation and Action of the Immunomodulator FTY720 Inhibits Vascular Endothelial Cell Growth Factor-induced Vascular Permeability
Open accessAbstract
FTY720, a potent immunosuppressive agent, is phosphorylated in vivo into FTY720-P, a high affinity agonist for sphingosine 1-phosphate (S1P) receptors. The effects of FTY720 on vascular cells, a major target of S1P action, have not been addressed. We now report the metabolic activation of FTY720 by sphingosine kinase-2 and potent activation of vascular endothelial cell functions in vitro and in vivo by phosphorylated FTY720 (FTY720-P). Incubation of endothelial cells with FTY720 resulted in phosphorylation by sphingosine kinase activity and formation of FTY720-P. Sphingosine kinase-2 effectively phosphorylated FTY720 in the human embryonic kidney 293T heterologous expression system. FTY720-P treatment of endothelial cells stimulated extracellular signal-activated kinase and Akt phosphorylation and adherens junction assembly and promoted cell survival. The effects of FTY720-P were inhibited by pertussis toxin, suggesting the requirement for Gi-coupled S1P receptors. Indeed, transmonolayer permeability induced by vascular endothelial cell growth factor was potently reversed by FTY720-P. Furthermore, oral FTY720 administration in mice potently blocked VEGF-induced vascular permeability in vivo. These findings suggest that FTY720 or its analogs may find utility in the therapeutic regulation of vascular permeability, an important process in angiogenesis, inflammation, and pathological conditions such as sepsis, hypoxia, and solid tumor growth.
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Cites
The biology of VEGF and its receptors
Ferrara, N., Gerber, H.-P., & LeCouter, J. (2003) · Nature Medicine · doi:10.1038/nm0603-669 · Cited by 9,591
Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm
Springer, T. A. (1994) · Cell · doi:10.1016/0092-8674(94)90337-9 · Cited by 6,929
Sphingosine-1-phosphate: an enigmatic signalling lipid
Spiegel, S., & Milstien, S. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1103 · Cited by 2,075
Alteration of Lymphocyte Trafficking by Sphingosine-1-Phosphate Receptor Agonists
Mandala, S., Hajdu, R., Bergstrom, J., Quackenbush, E., Xie, J., Milligan, J., Thornton, R., Shei, G.-J., Card, D., Keohane, C., et al. (2002) · Science · doi:10.1126/science.1070238 · Cited by 1,690
Suppression of ceramide-mediated programmed cell death by sphingosine-1-phosphate
Cuvillier, O., Pirianov, G., Kleuser, B., Vanek, P. G., Coso, O. A., Gutkind, J. S., & Spiegel, S. (1996) · Nature · doi:10.1038/381800a0 · Cited by 1,529
The Immune Modulator FTY720 Targets Sphingosine 1-Phosphate Receptors
Brinkmann, V., Davis, M. D., Heise, C. E., Albert, R., Cottens, S., Hof, R., Bruns, C., Prieschl, E., Baumruker, T., Hiestand, P., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c200176200 · Cited by 1,504
Self-citationLiu, Y., Wada, R., Yamashita, T., Mi, Y., Deng, C.-X., Hobson, J. P., Rosenfeldt, H. M., Nava, V. E., Chae, S.-S., Lee, M.-J., et al. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10905 · Cited by 1,149
Self-citationLee, M.-J., Thangada, S., Claffey, K. P., Ancellin, N., Liu, C. H., Kluk, M., Volpi, M., Sha'afi, R. I., & Hla, T. (1999) · Cell · doi:10.1016/s0092-8674(00)81661-x · Cited by 1,013
Self-citationSphingosine-1-Phosphate as a Ligand for the G Protein-Coupled Receptor EDG-1
Lee, M.-J., Van Brocklyn, J. R., Thangada, S., Liu, C. H., Hand, A. R., Menzeleev, R., Spiegel, S., & Hla, T. (1998) · Science · doi:10.1126/science.279.5356.1552 · Cited by 1,007
Self-citationSphingosine-1-phosphate as second messenger in cell proliferation induced by PDGF and FCS mitogens
Olivera, A., & Spiegel, S. (1993) · Nature · doi:10.1038/365557a0 · Cited by 889
Cited by
Signaling Mechanisms Regulating Endothelial Permeability
Mehta, D., & Malik, A. B. (2006) · Physiological Reviews · doi:10.1152/physrev.00012.2005 · Cited by 1,720
Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis
Brinkmann, V., Billich, A., Baumruker, T., Heining, P., Schmouder, R., Francis, G., Aradhye, S., & Burtin, P. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3248 · Cited by 1,273
Self-citationChemokines, sphingosine-1-phosphate, and cell migration in secondary lymphoid organs
Cyster, J. G. (2005) · Annual Review of Immunology · doi:10.1146/annurev.immunol.23.021704.115628 · Cited by 856
Sphingosine 1-phosphate and cancer
Pyne, N. J., & Pyne, S. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2875 · Cited by 852
Sphingosine 1-phosphate and its receptors: an autocrine and paracrine network
Rosen, H., & Goetzl, E. J. (2005) · Nature Reviews Immunology · doi:10.1038/nri1650 · Cited by 694
Metadata
- Authors
- Sanchez, T., Estrada-Hernandez, T., Paik, J.-H., Wu, M.-T., Venkataraman, K., Brinkmann, V., Claffey, K., & Hla, T.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-11
- Volume
- 278
- Issue
- 47
- Pages
- 47281-47290
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1984179269
- Cited by
- 374
- References
- 52
- FWCI
- 8.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Sanchez, T., Estrada-Hernandez, T., Paik, J.-H., Wu, M.-T., Venkataraman, K., Brinkmann, V., Claffey, K., & Hla, T. (2003). Phosphorylation and Action of the Immunomodulator FTY720 Inhibits Vascular Endothelial Cell Growth Factor-induced Vascular Permeability. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m306896200
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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