Integrin 3 1-dependent -catenin phosphorylation links epithelial Smad signaling to cell contacts

Pulmonary and Critical Care Division, Department of Medicine, and Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
The Journal of Cell Biology (Impact Factor: 9.83). 02/2009; 184(2):309-22. DOI: 10.1083/jcb.200806067
Source: PubMed


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, alpha3beta1, were found to have a markedly blunted EMT response to TGF-beta1. A mechanism for this defect was explored in alpha3-null cells reconstituted with wild-type (wt) alpha3 or point mutants unable to engage laminin 5 (G163A) or epithelial cadherin (E-cadherin; H245A). After TGF-beta1 stimulation, wt epithelial cells but not cells expressing the H245A mutant internalize complexes of E-cadherin and TGF-beta1 receptors, generate phospho-Smad2 (p-Smad2)-pY654-beta-catenin complexes, and up-regulate mesenchymal target genes. Although Smad2 phosphorylation is normal, p-Smad2-pY654-beta-catenin complexes do not form in the absence of alpha3 or when alpha3beta1 is mainly engaged on laminin 5 or E-cadherin in adherens junctions, leading to attenuated EMT. These findings demonstrate that alpha3beta1 coordinates cross talk between beta-catenin and Smad signaling pathways as a function of extracellular contact cues and thereby regulates responses to TGF-beta1 activation.

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Available from: Xiaopeng Li, Aug 15, 2014
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    • "This morphologic transformation was observed in the absence of BDNF addition in independent clones expressing TrkB, and was neither observed in the empty vector clones nor in the clones expressing kinase-inactive TrkB (Figure 4A and B). In order to exclude the possibility that unwanted alterations that inhibited declustering had occurred in any of the cell clones during selection or passaging, cells were also grown on fibronectin which leads to cell dispersal and EMT in primary alveolar epithelial cells as reported previously [32]. Culturing the cell clones on fibronectin revealed a similar extent of cell dispersal in all clones arguing against passaging-induced alterations (Figure 4A). "
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    Full-text · Article · Jun 2014 · PLoS ONE
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