Abstract
Transforming growth factor-β (TGF-β) signals by contacting two distantly related transmem-brane serine/threonine kinases called receptors I and II. The role of these molecules in signalling has now been determined. TGF-β binds directly to receptor II, which is a constitutively active kinase. Bound TGF-β is then recognized by receptor I which is recruited into the complex and becomes phosphorylated by receptor II. Phosphorylation allows receptor I to propagate the signal to downstream substrates. This provides a mechanism by which a cytokine can generate the first step of a signalling cascade.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
196,21 € per year
only 3,85 € per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
References
Massagué, J., Attisano, L. & Wrana, J. L. Trends Cell Biol. 4, 172–178 (1994).
Kingsley, D. M. Genes Dev. 8, 133–146 (1994).
Roberts, A. B. & Sporn, M. B. Growth Factors 8, 1–9 (1993).
Attisano, L., Wrana, J. L., López-Casillas, F. & Massagué, J. Biochim. biophys. Acta 1222, 71–80 (1994).
Lyons, K. M., Jones, C. M. & Hogan, B. L. M. Trends Genet, 7, 408–412 (1991).
Moses, H. L., Yang, E. Y. & Pietenpol, J. A. Cell 63, 245–247 (1990).
Border, W. A. & Ruoslahti, E. J. clin. Invest. 90, 1–7 (1992).
Mathews, L. S. & Vale, W. W. Cell 65, 973–982 (1991).
Attisano, L., Wrana, J. L., Cheifetz, S. & Massagué, J. Cell 68, 97–108 (1992).
Mathews, L. S., Vale, W. W. & Kintner, C. R. Science 255, 1702–1705 (1992).
Lin, H. Y., Wang, X.-F., Ng-Eaton, E., Weinberg, R. & Lodish, H. Cell 68, 775–785 (1992).
López-Casillas, F. et al. Cell 67, 785–795 (1991).
Wang, X.-F. et al. Cell 67, 797–805 (1991).
Estevez, M. et al. Nature 365, 644–649 (1993).
Childs, S. R. et al. Proc. natn. Acad. Sci. U.S.A. 90, 9475–9479 (1993).
Ebner, S. R. et al. Science 260, 1344–1348 (1993).
Attisano, L. et al. Cell 75, 671–680 (1993).
Franzén, P. et al. Cell 75, 681–692 (1993).
Tsuchida, K., Mathews, L. S. & Vale, W. W. Proc. natn. Acad. Sci. U.S.A. 90, 11242–11246 (1993).
Bassing, C. H. et al. Science 263, 87–89 (1994).
Wrana, J. L. et al. Molec. cell. Biol. 14, 944–950 (1994).
Laiho, M., Weis, F. M. B., Boyd, F. T., Ignotz, R. A. & Massagué, J. J. biol. Chem. 266, 9108–9112 (1991).
Wrana, J. L. et al. Cell 71, 1003–1014 (1992).
Inagaki, M., Moustakas, A., Lin, H. Y., Lodish, H. F. & Carr, B. I. Proc. natn. Acad. Sci. U.S.A. 90, 5359–5363 (1993).
Lin, H. Y. & Lodish, H. F. Trends Cell Biol. 3, 14–19 (1993).
Cárcamo, J. et al. Molec. cell. Biol. 14, 3810–3821 (1994).
Koenig, B. B. et al. Molec. cell. Biol. (in the press).
Ebner, R., Chen, R.-H., Lawler, S., Zioncheck, T. & Derynck, R. Science 262, 900–902 (1993).
ten Dijke, P. et al. Science 264, 101–104 (1994).
Ullrich, A. & Schlessinger, J. Cell 61, 203–212 (1990).
Pawson, T. Curr. Opin. Genet. Dev. 2, 4–12 (1992).
Lange-Carter, C. A., Pleiman, C. M., Gardner, A. M., Blumer, K. J. & Johnson, G. L. Science 260, 315–319 (1993).
Cheifetz, S. et al. J. biol. Chem. 265, 20533–20538 (1990).
Laiho, M., Weis, F. M. B. & Massagué, J. J. biol. Chem. 265, 18518–18524 (1990).
Wieser, R., Attisano, L., Wrana, J. L. & Massagué, J. Molec. cell. Biol. 13, 7239–7247 (1993).
Boyd, F. T. & Massagué, J. J. biol. Chem. 264, 2272–2278 (1989).
Stahl, N. & Yancopoulos, G. D. Cell 74, 587–590 (1993).
Mathews, L. S. & Vale, W. W. J. biol. Chem. 268, 19013–19018 (1993).
Massagué, J. Meth. Enzym. 146, 174–195 (1987).
Marshall, C. J. Nature 367, 686 (1994).
Boyle, W. J., van der Geer, P. & Hunter, T. Meth. Enzym. 201B, 110–149 (1991).
López-Casillas, F., Wrana, J. L. & Massagué, J. Cell 73, 1435–1444 (1993).
Schagger, H. & von Jagow, G. Analyt. Biochem. 166, 368–379 (1987).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Wrana, J., Attisano, L., Wieser, R. et al. Mechanism of activation of the TGF-β receptor. Nature 370, 341–347 (1994). https://doi.org/10.1038/370341a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/370341a0
This article is cited by
-
The endocannabinoid system promotes hepatocyte progenitor cell proliferation and maturation by modulating cellular energetics
Cell Death Discovery (2023)
-
Mechanisms of myeloid cell entry to the healthy and diseased central nervous system
Nature Immunology (2023)
-
Dedicated macrophages organize and maintain the enteric nervous system
Nature (2023)
-
RNF12 is regulated by AKT phosphorylation and promotes TGF-β driven breast cancer metastasis
Cell Death & Disease (2022)
-
Assessment of the TGFB1 gene expression and methylation status of the promoter region in patients with colorectal cancer
Scientific Reports (2022)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.