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

研究成果: Article

374 引用 (Scopus)

抜粋

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.

元の言語English
ページ(範囲)980-993
ページ数14
ジャーナルCell
131
発行部数5
DOI
出版物ステータスPublished - 2007 11 30
外部発表Yes

    フィンガープリント

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

これを引用

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