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

Luis C. Fuentealba, Edward Eivers, Atsushi Ikeda, Cecilia Hurtado, Hiroki Kuroda, Edgar M. Pera, Edward M. De Robertis

Research output: Contribution to journalArticle

371 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)980-993
Number of pages14
JournalCell
Volume131
Issue number5
DOIs
Publication statusPublished - 2007 Nov 30
Externally publishedYes

    Fingerprint

Keywords

  • CELLBIO
  • DEVBIO
  • SIGNALING

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Fuentealba, L. C., Eivers, E., Ikeda, A., Hurtado, C., Kuroda, H., Pera, E. M., & De Robertis, E. M. (2007). Integrating Patterning Signals: Wnt/GSK3 Regulates the Duration of the BMP/Smad1 Signal. Cell, 131(5), 980-993. https://doi.org/10.1016/j.cell.2007.09.027