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Integrating Patterning Signals: Wnt/GSK3 Regulates the Duration of the BMP/Smad1 Signal.

Fuentealba LC, LC; Eivers, E; Ikeda, A; Hurtado, C; Kuroda, H; Pera, Edgar LU and De Robertis, EM (2007) In Cell 131(5). p.980-993
Abstract
BMP receptors determine the intensity of BMP signals via Smad1 C-terminal phosphorylations. Here we show that a finely controlled cell biological pathway terminates this activity. The duration of the activated pSmad1Cter signal was regulated by sequential Smad1 linker region phosphorylations at conserved MAPK and GSK3 sites required for its polyubiquitinylation and transport to the centrosome. Proteasomal degradation of activated Smad1 and total polyubiquitinated proteins took place in the centrosome. Inhibitors of the Erk, p38, and JNK MAPKs, as well as GSK3 inhibitors, prolonged the duration of a pulse of BMP7. Wnt signaling decreased pSmad1GSK3 antigen levels and redistributed it from the centrosome to cytoplasmic LRP6 signalosomes. In... (More)
BMP receptors determine the intensity of BMP signals via Smad1 C-terminal phosphorylations. Here we show that a finely controlled cell biological pathway terminates this activity. The duration of the activated pSmad1Cter signal was regulated by sequential Smad1 linker region phosphorylations at conserved MAPK and GSK3 sites required for its polyubiquitinylation and transport to the centrosome. Proteasomal degradation of activated Smad1 and total polyubiquitinated proteins took place in the centrosome. Inhibitors of the Erk, p38, and JNK MAPKs, as well as GSK3 inhibitors, prolonged the duration of a pulse of BMP7. Wnt signaling decreased pSmad1GSK3 antigen levels and redistributed it from the centrosome to cytoplasmic LRP6 signalosomes. In Xenopus embryos, it was found that Wnts induce epidermis and that this required an active BMP-Smad pathway. Epistatic experiments suggested that the dorsoventral (BMP) and anteroposterior (Wnt/GSK3) patterning gradients are integrated at the level of Smad1 phosphorylations during embryonic pattern formation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cell
volume
131
issue
5
pages
980 - 993
publisher
Cell Press
external identifiers
  • Scopus:36248995245
ISSN
1097-4172
DOI
10.1016/j.cell.2007.09.027
language
English
LU publication?
yes
id
61a24663-bd99-4244-9588-56a765f57761 (old id 1141513)
date added to LUP
2008-08-12 14:22:28
date last changed
2016-11-27 04:36:21
@misc{61a24663-bd99-4244-9588-56a765f57761,
  abstract     = {BMP receptors determine the intensity of BMP signals via Smad1 C-terminal phosphorylations. Here we show that a finely controlled cell biological pathway terminates this activity. The duration of the activated pSmad1Cter signal was regulated by sequential Smad1 linker region phosphorylations at conserved MAPK and GSK3 sites required for its polyubiquitinylation and transport to the centrosome. Proteasomal degradation of activated Smad1 and total polyubiquitinated proteins took place in the centrosome. Inhibitors of the Erk, p38, and JNK MAPKs, as well as GSK3 inhibitors, prolonged the duration of a pulse of BMP7. Wnt signaling decreased pSmad1GSK3 antigen levels and redistributed it from the centrosome to cytoplasmic LRP6 signalosomes. In Xenopus embryos, it was found that Wnts induce epidermis and that this required an active BMP-Smad pathway. Epistatic experiments suggested that the dorsoventral (BMP) and anteroposterior (Wnt/GSK3) patterning gradients are integrated at the level of Smad1 phosphorylations during embryonic pattern formation.},
  author       = {Fuentealba LC, LC and Eivers, E and Ikeda, A and Hurtado, C and Kuroda, H and Pera, Edgar and De Robertis, EM},
  issn         = {1097-4172},
  language     = {eng},
  number       = {5},
  pages        = {980--993},
  publisher    = {ARRAY(0xa032728)},
  series       = {Cell},
  title        = {Integrating Patterning Signals: Wnt/GSK3 Regulates the Duration of the BMP/Smad1 Signal.},
  url          = {http://dx.doi.org/10.1016/j.cell.2007.09.027},
  volume       = {131},
  year         = {2007},
}