Send to:

Choose Destination
See comment in PubMed Commons below
FEBS Lett. 2005 Jul 4;579(17):3539-46.

Cross-talk between the TGFbeta and Wnt signaling pathways in murine embryonic maxillary mesenchymal cells.

Author information

  • 1University of Louisville Birth Defects Center, Department of Molecular, Cellular, and Craniofacial Biology, 501 South Preston Street, Suite 301, Louisville, KY 40292, United States.


The transforming growth factor beta (TGFbeta) and Wnt signaling pathways play central roles regulating embryogenesis and maintaining adult tissue homeostasis. TGFbeta mediates its cellular effects through types I and II cell surface receptors coupled to the nucleocytoplasmic Smad proteins. Wnt signals via binding to a cell surface receptor, Frizzled, which in turn activates intracellular Dishevelled, ultimately leading to stabilization and nuclear translocation of beta-catenin. Previous studies have demonstrated several points of cross-talk between the TGFbeta and Wnt signaling pathways. In yeast two-hybrid and GST-pull down assays, Dishevelled-1 and Smad 3 have been shown to physically interact through the C-terminal one-half of Dishevelled-1 and the MH2 domain of Smad 3. The current study demonstrates that co-treatment of murine embryonic maxillary mesenchyme (MEMM) cells with Wnt-3a and TGFbeta leads to enhanced reporter activity from TOPflash, a Wnt-responsive reporter plasmid. Transcriptional cooperation between TGFbeta and Wnt did not require the presence of a Smad binding element, nor did it occur when a TGFbeta-responsive reporter plasmid (p3TP-lux) was transfected. Overexpression of Smad 3 further enhanced the cooperation between Wnt and TGFbeta while overexpression of dominant-negative Smads 2 and 3 inhibited this effect. Co-stimulation with TGFbeta led to greater nuclear translocation of beta-catenin, providing explanation for the effect of TGFbeta on Wnt-3a reporter activity. Wnt-3a exerted antiproliferative activity in MEMM cells, similar to that exerted by TGFbeta. In addition, Wnt-3a and TGFbeta in combination led to synergistic decreases in MEMM cell proliferation. These data demonstrate a functional interaction between the TGFbeta and Wnt signaling pathways and suggest that Wnt activation of the canonical pathway is an important mediator of MEMM cell growth.

[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk