title: Acetaldehyde dissociates the PTP1B-E-cadherin-beta-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.
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, University of Memphis, Memphis, TN 38163, USA.
authors.forename: Parimal
authors.initials: P
authors.lastname: Sheth
authors.forename: Ankur
authors.initials: A
authors.lastname: Seth
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Atkinson
authors.forename: Tarun
authors.initials: T
authors.lastname: Gheyi
authors.forename: Gautam
authors.initials: G
authors.lastname: Kale
authors.forename: Francesco
authors.initials: F
authors.lastname: Giorgianni
authors.forename: Dominic M
authors.initials: DM
authors.lastname: Desiderio
authors.forename: Chunying
authors.initials: C
authors.lastname: Li
authors.forename: Anjaparavanda
authors.initials: A
authors.lastname: Naren
authors.forename: Radhakrishna
authors.initials: R
authors.lastname: Rao
mesh_terms: D000079:Acetaldehyde / Q000494:pharmacology*; D022005:Adherens Junctions / Q000187:drug effects / Q000378:metabolism; D000595:Amino Acid Sequence; D018938:Caco-2 Cells; D015820:Cadherins / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D062793:Occludin; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D015820:Cadherins; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D000079:Acetaldehyde