Smad7 stabilizes beta-catenin binding to E-cadherin complex and promotes cell-cell adhesion.
Beta-catenin functions both as an adherens junction adhesion protein and as an essential mediator of the canonical Wnt signaling pathway. Wnts stabilize beta-catenin and promote its accumulation in the nucleus, where it regulates transcription of the target genes. Here we show that Smad7 promotes cell-cell adhesion by stabilizing beta-catenin and ... consequently increases the beta-catenin-E-cadherin complex level at the plasma membrane. A Smad7-Axin interaction disassociates GSK-3beta and beta-catenin from Axin, as well as inhibits the recruitment of Smurf2, an E3 ligase, to beta-catenin, thus protecting beta-catenin from phosphorylation and degradation. Smad7 increases the stabilized beta-catenin to form a complex with E-cadherin and stabilizes the E-cadherin-beta-catenin complex. Thereby, rather than being translocated to the nucleus for regulating the target gene transcription, Smad7-stabilized-beta-catenin is shunted to the E-cadherin complex to modulate cell-cell adhesion.
Mesh Terms:
Active Transport, Cell Nucleus, Animals, Axin Protein, Cadherins, Cell Adhesion, Cell Line, Cell Membrane, Cell Nucleus, Glycogen Synthase Kinase 3, Humans, Mice, Multiprotein Complexes, Phosphorylation, Protein Binding, Repressor Proteins, Smad7 Protein, Ubiquitin-Protein Ligases, Wnt Proteins, beta Catenin
Active Transport, Cell Nucleus, Animals, Axin Protein, Cadherins, Cell Adhesion, Cell Line, Cell Membrane, Cell Nucleus, Glycogen Synthase Kinase 3, Humans, Mice, Multiprotein Complexes, Phosphorylation, Protein Binding, Repressor Proteins, Smad7 Protein, Ubiquitin-Protein Ligases, Wnt Proteins, beta Catenin
J. Biol. Chem.
Date: Aug. 29, 2008
PubMed ID: 18593713
View in: Pubmed Google Scholar
Download Curated Data For This Publication
147541
Switch View:
- Interactions 5
- PTM Genes 1