The Tumor Suppressor Smad4/DPC4 Is Regulated by Phosphorylations that Integrate FGF, Wnt, and TGF-β Signaling

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The Tumor Suppressor Smad4/DPC4 Is Regulated by Phosphorylations that Integrate FGF, Wnt, and TGF-β Signaling

Authors
Type
Published Article
Journal
Cell Reports
Publisher
Elsevier
Volume
9
Issue
2
Pages
688–700
Identifiers
DOI: 10.1016/j.celrep.2014.09.020
Source
CdV-UPMC
License
Unknown

Abstract

Graphical Abstract Highlights The tumor suppressor Smad4 is regulated by FGF/MAPK and Wnt/GSK3 phosphorylations Sequential phosphorylations control both Smad4 activity and degradation by b-TrCP In the presence of FGF, Wnt potentiates TGF-b at low physiolog-ical concentrations This mechanism controls germ layer and organizer specification in Xenopus In Brief Demagny et al. show that Smad4 is phos-phorylated after FGF primes three inhibi-tory phosphorylations by GSK3. In the presence of FGF and Wnt, signaling by low concentrations of TGF-b is greatly enhanced, helping explain the devas-tating effects of loss of the tumor sup-pressor Smad4.

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