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Cell 2007 Nov 30;1315:980-93. doi: 10.1016/j.cell.2007.09.027.
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Integrating patterning signals: Wnt/GSK3 regulates the duration of the BMP/Smad1 signal.

Fuentealba LC , Eivers E , Ikeda A , Hurtado C , Kuroda H , Pera EM , De Robertis EM .

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 pSmad1(Cter) 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 pSmad1(GSK3) 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.

PubMed ID: 18045539
PMC ID: PMC2200633
Article link: Cell
Grant support: [+]

Species referenced: Xenopus
Genes referenced: admp bmp4 bmp7.1 bmp7.2 chrd dkk1 grap2 gsk3b krt12.4 lrp6 mad1l1 mapk1 mapk14 mapk8 myod1 odc1 smad1 smurf1 sox2 szl tbx2 tcf3 tcf7l1 wnt3a wnt8a
Morpholinos: wnt8a MO3

Article Images: [+] show captions
References [+] :
Aubert, Functional gene screening in embryonic stem cells implicates Wnt antagonism in neural differentiation. 2002, Pubmed