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- Title
Integrin α3β1-dependent β-catenin phosphorylation links epithelial Smad signaling to cell contacts.
- Authors
Young Kim; Kugler, Matthias C.; Ying Wei; Kim, Kevin K.; Xiaopeng Li; Brumwell, Alexis N.; Chapman, Harold A.
- Abstract
Injury-initiated epithelial to mesenchymal transition (EMT) depends on contextual signals from the extracellular matrix, suggesting a role for integrin signaling. Primary epithelial cells deficient in their prominent laminin receptor, α3β1, were found to have a markedly blunted EMT response to TGF-β1. A mechanism for this defect was explored in α3-null cells reconstituted with wild-type (wt) α3 or point mutants unable to engage laminin 5 (G163A) or epithelial cadherin (E-cadherin; H245A). After TGF-β1 stimulation, wt epithelial cells but not cells expressing the H245A mutant internalize complexes of E-cadherin and TGF-β1 receptors, generate phospho-Smad2 (p-Smad2)-pY654-β-catenin complexes, and upregulate mesenchymal target genes. Although Smad2 phosphorylation is normal, p-Smad2-pY654-β-catenin complexes do not form in the absence of α3 or when α3β1 is mainly engaged on laminin 5 or E-cadherin in adherens junctions, leading to attenuated EMT. These findings demonstrate that α3β1 coordinates cross talk between β-catenin and Smad signaling pathways as a function of extracellular contact cues and thereby regulates responses to TGF-β1 activation.
- Publication
Journal of Cell Biology, 2009, Vol 184, Issue 2, p309
- ISSN
0021-9525
- Publication type
Academic Journal
- DOI
10.1083/jcb.200806067