Balancing the activation state of the endothelium via two distinct TGF-beta type I receptors
(2002) In EMBO Journal 21(7). p.1743-1753- Abstract
- The generation of mice lacking specific components of the transforming growth factor-beta (TGF-beta) signal tranduction pathway shows that TGF-beta is a key player in the development and physiology of the cardiovascular system. Both pro- and anti-angiogenic properties have been ascribed to TGF-beta, for which the molecular mechanisms are unclear. Here we report that TGF-beta can activate two distinct type I receptor/Smad signalling pathways with opposite effects. TGF-beta induces phosphorylation of Smad1/5 and Smad2 in endothelial cells and these effects can be blocked upon selective inhibition of ALK1 or ALK5 expression, respectively. Whereas the TGF-beta/ALK5 pathway leads to inhibition of cell migration and proliferation, the TGF-beta/... (More)
- The generation of mice lacking specific components of the transforming growth factor-beta (TGF-beta) signal tranduction pathway shows that TGF-beta is a key player in the development and physiology of the cardiovascular system. Both pro- and anti-angiogenic properties have been ascribed to TGF-beta, for which the molecular mechanisms are unclear. Here we report that TGF-beta can activate two distinct type I receptor/Smad signalling pathways with opposite effects. TGF-beta induces phosphorylation of Smad1/5 and Smad2 in endothelial cells and these effects can be blocked upon selective inhibition of ALK1 or ALK5 expression, respectively. Whereas the TGF-beta/ALK5 pathway leads to inhibition of cell migration and proliferation, the TGF-beta/ ALK1 pathway induces endothelial cell migration and proliferation. We identified genes that are induced specifically by TGF-beta-mediated ALK1 or ALK5 activation. Id1 was found to mediate the TGF-beta/ALK1-induced (and Smad-dependent) migration, while induction of plasminogen activator inhibitor-1 by activated ALK5 may contribute to the TGF-beta-induced maturation of blood vessels. Our results suggest that TGF-beta regulates the activation state of the endothelium via a fine balance between ALK5 and ALK1 signalling. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/340372
- author
- Goumans, MJ ; Valdimarsdottir, G ; Itoh, S ; Rosendahl, A ; Sideras, Paschalis LU and ten Dijke, P
- organization
- publishing date
- 2002
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- signal transduction, ALK, angiogenesis, Smad, TGF-beta
- in
- EMBO Journal
- volume
- 21
- issue
- 7
- pages
- 1743 - 1753
- publisher
- Oxford University Press
- external identifiers
-
- wos:000174992000024
- pmid:11927558
- scopus:0037007226
- ISSN
- 1460-2075
- DOI
- 10.1093/emboj/21.7.1743
- language
- English
- LU publication?
- yes
- id
- f4d3f6cb-7b84-4014-906c-423a329c6c55 (old id 340372)
- date added to LUP
- 2016-04-01 15:24:31
- date last changed
- 2022-04-22 07:31:26
@article{f4d3f6cb-7b84-4014-906c-423a329c6c55,
abstract = {{The generation of mice lacking specific components of the transforming growth factor-beta (TGF-beta) signal tranduction pathway shows that TGF-beta is a key player in the development and physiology of the cardiovascular system. Both pro- and anti-angiogenic properties have been ascribed to TGF-beta, for which the molecular mechanisms are unclear. Here we report that TGF-beta can activate two distinct type I receptor/Smad signalling pathways with opposite effects. TGF-beta induces phosphorylation of Smad1/5 and Smad2 in endothelial cells and these effects can be blocked upon selective inhibition of ALK1 or ALK5 expression, respectively. Whereas the TGF-beta/ALK5 pathway leads to inhibition of cell migration and proliferation, the TGF-beta/ ALK1 pathway induces endothelial cell migration and proliferation. We identified genes that are induced specifically by TGF-beta-mediated ALK1 or ALK5 activation. Id1 was found to mediate the TGF-beta/ALK1-induced (and Smad-dependent) migration, while induction of plasminogen activator inhibitor-1 by activated ALK5 may contribute to the TGF-beta-induced maturation of blood vessels. Our results suggest that TGF-beta regulates the activation state of the endothelium via a fine balance between ALK5 and ALK1 signalling.}},
author = {{Goumans, MJ and Valdimarsdottir, G and Itoh, S and Rosendahl, A and Sideras, Paschalis and ten Dijke, P}},
issn = {{1460-2075}},
keywords = {{signal transduction; ALK; angiogenesis; Smad; TGF-beta}},
language = {{eng}},
number = {{7}},
pages = {{1743--1753}},
publisher = {{Oxford University Press}},
series = {{EMBO Journal}},
title = {{Balancing the activation state of the endothelium via two distinct TGF-beta type I receptors}},
url = {{http://dx.doi.org/10.1093/emboj/21.7.1743}},
doi = {{10.1093/emboj/21.7.1743}},
volume = {{21}},
year = {{2002}},
}