Acetaldehyde dissociates the PTP1B–E-cadherin–β-catenin complex in Caco-2 cell monolayers by a phosphorylation-dependent mechanism

Abstract

Interactions between E-cadherin, beta-catenin and PTP1B (protein tyrosine phosphatase 1B) are crucial for the organization of AJs (adherens junctions) and epithelial cell-cell adhesion. In the present study, the effect of acetaldehyde on the AJs and on the interactions between E-cadherin, beta-catenin and PTP1B was determined in Caco-2 cell monolayers. Treatment of cell monolayers with acetaldehyde induced redistribution of E-cadherin and beta-catenin from the intercellular junctions by a tyrosine phosphorylation-dependent mechanism. The PTPase activity associated with E-cadherin and beta-catenin was significantly reduced and the interaction of PTP1B with E-cadherin and beta-catenin was attenuated by acetaldehyde. Acetaldehyde treatment resulted in phosphorylation of beta-catenin on tyrosine residues, and abolished the interaction of beta-catenin with E-cadherin by a tyrosine kinase-dependent mechanism. Protein binding studies showed that the treatment of cells with acetaldehyde reduced the binding of beta-catenin to the C-terminal region of E-cadherin. Pairwise binding studies using purified proteins indicated that the direct interaction between E-cadherin and beta-catenin was reduced by tyrosine phosphorylation of beta-catenin, but was unaffected by tyrosine phosphorylation of E-cadherin-C. Treatment of cells with acetaldehyde also reduced the binding of E-cadherin to GST (glutathione S-transferase)-PTP1B. The pairwise binding study showed that GST-E-cadherin-C binds to recombinant PTP1B, but this binding was significantly reduced by tyrosine phosphorylation of E-cadherin. Acetaldehyde increased the phosphorylation of beta-catenin on Tyr-331, Tyr-333, Tyr-654 and Tyr-670. These results show that acetaldehyde induces disruption of interactions between E-cadherin, beta-catenin and PTP1B by a phosphorylation-dependent mechanism.

Compromised E-cadherin adhesion and epithelial barrier function with activation of G protein-coupled receptors is rescued by Y-to-F mutations in β-catenin

“…PTP1B persistently dephosphorylates ␤-catenin tyrosines, enhancing binding of ␤-catenin to cadherin (2,25). This organization of regulatory molecules is consistent with a recent report that acetaldehyde disrupted the E-cadherin-␤-catenin complex in Caco-2 cells in a process dependent on tyrosine phosphorylation (18). In this report, tyrosine phosphorylation of E-cadherin was associated with interruption of the binding of PTP1B to E-cadherin with consequent increased tyrosine phosphorylation of ␤-catenin.…”

“…The tyrosine kinase Fer and the tyrosine phosphatase PTP1B are associated directly or indirectly with the cytoplasmic domain (2,18,25). Fer is responsible for tyrosine phosphorylation of PTP1B, a state necessary for PTP1B binding to cadherin (16,25).…”

Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and medical consequences: Summary of a symposium

“…Since interactions between E-cadherin, β-catenin and PTP1B are crucial for the organization of adherens junctions and epithelial cell-cell adhesion and subsequent maintenance of intestinal epithelial barrier, researchers further investigated the effect of acetaldehyde on the interactions between E-cadherin, β-catenin and PTP1B in Caco-2 cell monolayers (Sheth et al, 2007). In this study, investigators demonstrated that acetaldehyde induced disruption of interactions between E-cadherin, β-catenin and PTP1B by a phosphorylation-dependent mechanism, suggesting that this may be a mechanism whereby acetaldehyde impairs intestinal permeability.…”

Receptor protein tyrosine phosphatase RPTPα controls epithelial adherens junctions, linking E-cadherin engagement to c-Src signaling to cortactin

“…Inhibition of PTP activity by pervanadate treatment disrupts epithelial junctions and, interestingly, impairs E-cadherin-activated Src signaling . Although some studies have reported a role for cell-contact-associated PTPs in controlling the integrity and function of epithelial junctions (Anders et al, 2006;Espejo et al, 2010;Fuchs et al, 1996;Müller et al, 1999;Sheth et al, 2007), none of the identified PTPs has been shown to control junctional SFKs.…”