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Activin receptor-like kinase (ALK)1 is an antagonistic mediator of lateral TGFP/ALK5 signaling

Goumans, MJ ; Valdimarsdottir, G ; Itoh, S ; Lebrin, F ; Larsson, Jonas LU ; Mummery, C ; Karlsson, Stefan LU orcid and ten Dijke, P (2003) In Molecular Cell 12(4). p.817-828
Abstract
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... (More)
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. (Less)
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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Cell
volume
12
issue
4
pages
817 - 828
publisher
Cell Press
external identifiers
  • wos:000186196100007
  • pmid:14580334
  • scopus:0242330126
ISSN
1097-4164
DOI
10.1016/S1097-2765(03)00386-1
language
English
LU publication?
yes
id
c4cdd5c7-b5d2-48d6-9b28-ed624d18939d (old id 297110)
date added to LUP
2016-04-01 12:17:14
date last changed
2025-04-04 15:15:59
@article{c4cdd5c7-b5d2-48d6-9b28-ed624d18939d,
  abstract     = {{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.}},
  author       = {{Goumans, MJ and Valdimarsdottir, G and Itoh, S and Lebrin, F and Larsson, Jonas and Mummery, C and Karlsson, Stefan and ten Dijke, P}},
  issn         = {{1097-4164}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{817--828}},
  publisher    = {{Cell Press}},
  series       = {{Molecular Cell}},
  title        = {{Activin receptor-like kinase (ALK)1 is an antagonistic mediator of lateral TGFP/ALK5 signaling}},
  url          = {{http://dx.doi.org/10.1016/S1097-2765(03)00386-1}},
  doi          = {{10.1016/S1097-2765(03)00386-1}},
  volume       = {{12}},
  year         = {{2003}},
}