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Activin Receptor-like Kinase (ALK)1 Is an Antagonistic Mediator of Lateral TGFβ/ALK5 Signaling
Open accessAbstract
Transforming growth factor-beta (TGFbeta) regulates the activation state of the endothelium via two opposing type I receptor/Smad pathways. Activin receptor-like kinase-1 (ALK1) induces Smad1/5 phosphorylation, leading to an increase in endothelial cell proliferation and migration, while ALK5 promotes Smad2/3 activation and inhibits both processes. Here, we report that ALK5 is important for TGFbeta/ALK1 signaling; endothelial cells lacking ALK5 are deficient in TGFbeta/ALK1-induced responses. More specifically, we show that ALK5 mediates a TGFbeta-dependent recruitment of ALK1 into a TGFbeta receptor complex and that the ALK5 kinase activity is required for optimal ALK1 activation. TGFbeta type II receptor is also required for ALK1 activation by TGFbeta. Interestingly, ALK1 not only induces a biological response opposite to that of ALK5 but also directly antagonizes ALK5/Smad signaling.
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“and expression of angiogenic factors, including VEGF-A262,268.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [268]
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Cites
Massagué, J. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.753 · Cited by 7,571
A System for Stable Expression of Short Interfering RNAs in Mammalian Cells
Brummelkamp, T. R., Bernards, R., & Agami, R. (2002) · Science · doi:10.1126/science.1068999 · Cited by 4,295
A simplified system for generating recombinant adenoviruses
He, T., Zhou, S., da Costa, L. T., Yu, J., Kinzler, K. W., & Vogelstein, B. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.5.2509 · Cited by 3,209
Mechanism of activation of the TGF-β receptor
Wrana, J. L., Attisano, L., Wieser, R., Ventura, F., & Massagué, J. (1994) · Nature · doi:10.1038/370341a0 · Cited by 2,340
Dennler, S., Itoh, S., Vivien, D., ten Dijke, P., Huet, S., & Gauthier, J. (1998) · The EMBO Journal · doi:10.1093/emboj/17.11.3091 · Cited by 1,793
Self-citationInman, G. J., Nicolás, F. J., Callahan, J. F., Harling, J. D., Gaster, L. M., Reith, A. D., Laping, N. J., & Hill, C. S. (2002) · Molecular Pharmacology · doi:10.1124/mol.62.1.65 · Cited by 1,654
Balancing the activation state of the endothelium via two distinct TGF‐β type I receptors
Goumans, M., Valdimarsdóttir, G., Itoh, S., Rosendahl, A., Sideras, P., & ten Dijke, P. (2002) · The EMBO Journal · doi:10.1093/emboj/21.7.1743 · Cited by 1,127
Self-citationTGF‐β receptor‐mediated signalling through Smad2, Smad3 and Smad4
Nakao, A., Imamura, T., Souchelnytskyi, S., Kawabata, M., Ishisaki, A., Oeda, E., Tamaki, K., Hanai, J., Heldin, C., Miyazono, K., et al. (1997) · The EMBO Journal · doi:10.1093/emboj/16.17.5353 · Cited by 1,071
Miettinen, P. J., Ebner, R., Lopez, A. R., & Derynck, R. (1994) · The Journal of Cell Biology · doi:10.1083/jcb.127.6.2021 · Cited by 939
Korchynskyi, O., & ten Dijke, P. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111023200 · Cited by 876
Oh, S. P., Seki, T., Goss, K. A., Imamura, T., Yi, Y., Donahoe, P. K., Li, L., Miyazono, K., ten Dijke, P., Kim, S., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.6.2626 · Cited by 872
Physiological Actions and Clinical Applications of Transforming Growth Factor-β (TGF-β)
Roberts, A. B., & Sporn, M. B. (1993) · Growth Factors · doi:10.3109/08977199309029129 · Cited by 755
Transforming growth factor-beta: Vasculogenesis, angiogenesis, and vessel wall integrity
Pepper, M. S. (1997) · Cytokine & Growth Factor Reviews · doi:10.1016/s1359-6101(96)00048-2 · Cited by 737
Transforming Growth Factor‐β: Major Role in Regulation of Extracellular Matrix
ROBERTS, A. B., HEINE, U. I., FLANDERS, K. C., & SPORN, M. B. (1990) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1990.tb17931.x · Cited by 696
Wieser, R., Wrana, J. L., & Massagué, J. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb07214.x · Cited by 689
Attisano, L. (1993) · Cell · doi:10.1016/0092-8674(93)90488-c · Cited by 639
Jonk, L. J. C., Itoh, S., Heldin, C., ten Dijke, P., & Kruijer, W. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.33.21145 · Cited by 569
Self-citationAbnormal angiogenesis but intact hematopoietic potential in TGF‐β type I receptor‐deficient mice
Larsson, J., Goumans, M., Sjöstrand, L. J., van Rooijen, M. A., Ward, D., Levéen, P., Xu, X., ten Dijke, P., Mummery, C. L., & Karlsson, S. (2001) · The EMBO Journal · doi:10.1093/emboj/20.7.1663 · Cited by 563
Self-citationCharacterization of Type I Receptors for Transforming Growth Factor-β and Activin
ten Dijke, P., Yamashita, H., Ichijo, H., Franzèn, P., Laiho, M., Miyazono, K., & Heldin, C. (1994) · Science · doi:10.1126/science.8140412 · Cited by 551
Cloning of a Type I TGF-β Receptor and Its Effect on TGF-β Binding to the Type II Receptor
Ebner, R., Chen, R., Shum, L., et al. (1993) · Science · doi:10.1126/science.8388127 · Cited by 402
Functional analysis of the TGFbeta receptor/Smad pathway through gene ablation in mice
Goumans, M., & Mummery, C. L. (2000) · The International Journal of Developmental Biology · doi:10.1387/ijdb.10853822 · Cited by 376
Self-citationCárcamo, J. M., Weis‐Garcia, F., Ventura, F., Wieser, R., Wrana, J. L., Attisano, L., & Massagué, J. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.6.3810 · Cited by 373
Yamashita, H., ten Dijke, P., Franzèn, P., Miyazono, K., & Heldin, C. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)32142-7 · Cited by 326
Candia, A. F., Watabe, T., Hawley, S. H. B., Onichtchouk, D., Zhang, Y. E., Derynck, R., Niehrs, C., & Cho, K. W. Y. (1997) · Development · doi:10.1242/dev.124.22.4467 · Cited by 257
Smad1 Recognition and Activation by the ALK1 Group of Transforming Growth Factor-β Family Receptors
Chen, Y., & Massagué, J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.6.3672 · Cited by 217
Elucidation of Smad Requirement in Transforming Growth Factor-β Type I Receptor-induced Responses
Itoh, S., Thorikay, M., Kowanetz, M., Moustakas, A., Itoh, F., Heldin, C., & ten Dijke, P. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m208258200 · Cited by 211
Self-citationWeis‐Garcia, F., & Massagué, J. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00358.x · Cited by 158
Lux, A., Attisano, L., & Marchuk, D. A. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.15.9984 · Cited by 143
Luo, K., & Lodish, H. F. (1997) · The EMBO Journal · doi:10.1093/emboj/16.8.1970 · Cited by 126
Luo, K., & Lodish, H. F. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00826.x · Cited by 124
Hendrix, M. J. C., Seftor, R. E. B., Seftor, E. A., et al. (2002) · PubMed · Cited by 123
Silvestri, C., Bose, R., Attisano, L., & Wrana, J. L. (2010) · Elsevier eBooks · doi:10.1016/b978-0-12-374145-5.00070-x · Cited by 64
Altered expression of TGFB receptors and mitogenic effects of TGFB in pancreatic carcinomas
Jonson, T., Albrechtsson, E., Axelson, J., et al. (2001) · International Journal of Oncology · doi:10.3892/ijo.19.1.71 · Cited by 63
Localization of Transforming Growth Factor-β Type I and Type II Receptors in Mouse Development
Iseki, S., Osumi, N., Miyazono, K., et al. (1995) · Experimental Cell Research · doi:10.1006/excr.1995.1237 · Cited by 61
Yamane, A., Mayo, M. L., Bringas, P., Chen, L., Huynh, M., Thai, K., Shum, L., & Slavkin, H. C. (1997) · Developmental Dynamics · doi:10.1002/(sici)1097-0177(199708)209:4 · Cited by 24
Ward, S. M., Desgrosellier, J. S., Zhuang, X., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m209668200 · Cited by 16
Research works printed but not linked: 1
- Hendrix, 2002, Transendothelial function of human metastatic melanoma cells, Cancer Res., 62, 665
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Akhurst, R. J., & Hata, A. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3810 · Cited by 1,466
Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches
Guilliams, M., Bonnardel, J., Haest, B., Vanderborght, B., Wagner, C., Remmerie, A., Bujko, A., Martens, L., Thoné, T., Browaeys, R., et al. (2022) · Cell · doi:10.1016/j.cell.2021.12.018 · Cited by 985
TGFβ biology in cancer progression and immunotherapy
Derynck, R., Turley, S. J., & Akhurst, R. J. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0403-1 · Cited by 944
Endothelial-Mural Cell Signaling in Vascular Development and Angiogenesis
Gaengel, K., Genové, G., Armulik, A., & Betsholtz, C. (2009) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.107.161521 · Cited by 933
Signaling Receptors for TGF-β Family Members
Heldin, C.-H., & Moustakas, A. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a022053 · Cited by 711
Metadata
- Authors
- Goumans, M.-J., Valdimarsdottir, G., Itoh, S., Lebrin, F., Larsson, J., Mummery, C., Karlsson, S., & ten Dijke, P.
- Affiliations
- The Netherlands Cancer Institute (NL)
- Skåne University Hospital (SE)
- Hubrecht Institute for Developmental Biology and Stem Cell Research (NL)
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2003-10
- Volume
- 12
- Issue
- 4
- Pages
- 817-828
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W1978999523
- Cited by
- 689
- References
- 36
- Citations by year
- 2026: 9 · 2025: 17 · 2024: 23 · 2023: 21 · 2022: 21 · 2021: 27 · 2020: 27 · 2019: 23 · 2018: 22 · 2017: 22 · 2016: 26 · 2015: 36 · 2014: 29 · 2013: 46 · 2012: 40
- FWCI
- 10.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Kruppel-like factors research
- Keywords
- ALK1, ALK5, TGF-beta signaling, Smad1/5, Smad2/3, endothelial cells, TGFBR2, receptor complex assembly, kinase activity
- MeSH terms
- Receptor, Transforming Growth Factor-beta Type I, Receptor, Transforming Growth Factor-beta Type II, Animals, Cell Division, Cell Movement, DNA-Binding Proteins, Humans, Mutation, Phosphoproteins, Repressor Proteins, Transcription Factors, Signal Transduction, Trans-Activators, Transforming Growth Factor beta, Protein Serine-Threonine Kinases, Receptors, Transforming Growth Factor beta, COS Cells, Activin Receptors, Type I, Activin Receptors, Type II, Endothelial Cells, Cell Line, Tumor, Macromolecular Substances, Smad Proteins, Inhibitor of Differentiation Protein 1, Smad1 Protein, Smad5 Protein
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