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Cell Death Differ 2012 Oct 01;1910:1689-97. doi: 10.1038/cdd.2012.50.
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Signaling crosstalk between TGFβ and Dishevelled/Par1b.

Mamidi A , Inui M , Manfrin A , Soligo S , Enzo E , Aragona M , Cordenonsi M , Wessely O , Dupont S , Piccolo S .

Crosstalk of signaling pathways is critical during metazoan development and adult tissue homeostasis. Even though the transforming growth factor-beta (TGFβ) transduction cascade is rather simple, in vivo responsiveness to TGFβ ligands is tightly regulated at several steps. As such, TGFβ represents a paradigm for how the activity of one signaling system is modulated by others. Here, we report an unsuspected regulatory step involving Dishevelled (Dvl) and Par1b (also known as MARK2). Dvl and Par1b cooperate to enable TGFβ/bone morphogenetic protein (BMP) signaling in Xenopus mesoderm development and TGFβ responsiveness in mammalian cells. Mechanistically, the assembly of the Par1b/Dvl3/Smad4 complex is fostered by Wnt5a. The association of Smad4 to Dvl/Par1 prevents its inhibitory ubiquitination by ectodermin (also known as transcriptional intermediary factor 1 gamma or tripartite motif protein 33). We propose that this crosstalk is relevant to coordinate TGFβ responses with Wnt-noncanonical and polarity pathways.

PubMed ID: 22576663
PMC ID: PMC3438499
Article link: Cell Death Differ
Grant support: [+]

Species referenced: Xenopus
Genes referenced: babam2 bmp2 chrd.1 dvl1 dvl2 dvl3 f2r foxh1 id2 isyna1 junb mark2 mark3 mix1 myc nodal smad10 smad2 smad3 smad4 szl tbxt tgfbr1 tp53 trim33 usp9x vegt wnt5a
Morpholinos: ctnnb1 MO1 dvl2 MO1 dvl3 MO1 mark2 MO1 mark2 MO3

Phenotypes: Xla Wt + bmp2 + dvl3 MO (fig.S2.d) [+]

Article Images: [+] show captions
References [+] :
Adorno, A Mutant-p53/Smad complex opposes p63 to empower TGFbeta-induced metastasis. 2009, Pubmed