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

In English

Författare

  • LC Fuentealba LC
  • E Eivers
  • A Ikeda
  • C Hurtado
  • H Kuroda
  • Edgar Pera
  • EM De Robertis

Summary, in English

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.

Publiceringsår

2007

Språk

Engelska

Sidor

980-993

Publikation/Tidskrift/Serie

Cell

Volym

131

Issue

5

Dokumenttyp

Artikel i tidskrift

Förlag

Cell Press

Ämne

  • Cell and Molecular Biology

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1097-4172