Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:B0FTZ7 (catenin)
 18,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The E-cadherin/catenin complex is a calcium-dependent cell-cell adhesion molecule, whose function is critical to the integrity of the adherens junction and which plays a role in the establishment and maintenance of normal epithelial morphology and differentiation. Loss of E-cadherin-mediated adhesion appears to be a fundamental aspect of the neoplastic phenotype which in some cases appears to be mediated by post-translational modifications (i.e. tyrosine phosphorylation) of its interacting proteins, the catenins which link E-cadherin to the actin cytoskeleton. There is increasing experimental evidence to suggest that epidermal growth factor receptor tyrosine phosphorylation may lead to the inactivation of the E-cadherin/catenin complex in cancer cells through its interaction with beta- or gamma-catenin in the cytoskeleton. Modulation of epidermal growth factor receptor activity by pharmacological agents has the potential to regulate a variety of cellular processes including adhesion, differentiation, and proliferation.
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PMID:The E-cadherin/epidermal growth factor receptor interaction: a hypothesis of reciprocal and reversible control of intercellular adhesion and cell proliferation. 1036 89

Adherens junctions of the endothelium play a key role in the maintenance of endothelial permeability and are composed of the vascular endothelial (VE)-cadherin/catenin adhesion complex. We report that following tumour cell (MDA MB231 cells) adherence to the HUVECs, there was a rapid (within 5 min) redistribution of VE-cadherin, resulting in its transient loss from regions of endothelial cell-cell contact. The molecule gradually reorganised within the endothelial cell contacts after this time. It was further shown that the overall expression of VE-cadherin did not change, however, the amount of alpha- and beta-catenins coprecipitated with VE-cadherin markedly decreased after 5 min of tumour cell adhesion to the HUVECs. Immunoprobing of these samples with anti-phosphotyrosine antibodies demonstrated that the tyrosine phosphorylation of VE-cadherin was significantly increased following 5 min of tumour cell adhesion. Together, these results suggest that the adhesion of tumour cells to HUVEC promotes the redistribution of VE-cadherin from interendothelial adherens junctions, an effect that may be attributed to the increase in tyrosine phosphorylation of members of the VE-cadherin/catenin adhesion complex. This, in turn, may increase vascular endothelial permeability and facilitate the transendothelial migration of tumour cells during extravasation.
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PMID:Phosphorylation and disorganization of vascular-endothelial cadherin in interaction between breast cancer and vascular endothelial cells. 1040 88

Cell-cell contacts are important regulatory elements in tissue development, organ morphogenesis and malignant tumor invasion. In recent in vivo studies we have identified the members of the cadherin/catenin family of cell adhesion proteins that are differentially expressed in the pancreas and have determined their cell biological dynamics during dissociation and repair of adherens junctions. To further characterize these events, epithelial cell culture systems were used and a number of type II protein tyrosine phosphatases (PTPs) were found to colocalize and interact with the cadherin/catenin complex. These observations suggest that tyrosine dephosphorylation in general and PTPs in particular are involved in cell contact formation. Our most recent experiments indicate 1) that inhibition of PTPs alone dissociates pancreatic adherens junctions, 2) that cytosolic and transmembrane PTPs are differentially expressed in acinar cells, and 3) that a subset of them can associate with proteins of the cadherin/catenin complex at pancreatic cell-cell adhesions.
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PMID:Protein tyrosine dephosphorylation and the maintenance of cell adhesions in the pancreas. 1041 59

Tumour cell metastatic potential is significantly enhanced following treatment with HGF/SF, the ligand for the c-met receptor tyrosine kinase. Following c-met activation in tumour cells, phosphorylation of beta-catenin occurs, together with loss of intercellular adhesion and a gain in the motile and invasive nature of the cell. In this study we show that c-met is co-localised with beta-catenin and E-cadherin at regions of cell-cell contact in human colon cancer (HRT18 and HT115) and two breast cancer (MCF7 and MDA MB 231) cell lines. Immunoprecipitation studies demonstrated an association between c-met and members of the cadherin adhesion complex in these epithelial tumour cells, along with the membrane tyrosine protein phophatase, PTPmu. We conclude that the HGF/SF receptor, c-met, together with members of the cadherin/catenin cell-cell adhesion system and PTPmu, may form part of a protein complex in E-cadherin positive tumour cells that acts to regulate intercellular adhesion following HGF/SF stimulation.
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PMID:Association of the HGF/SF receptor, c-met, with the cell-surface adhesion molecule, E-cadherin, and catenins in human tumor cells. 1042 98

Catenins function as regulators of cellular signaling events in addition to their previously documented roles in adherens junction formation and function. Evidence to date suggests that beta and gamma catenins can act as signaling molecules, bind transcriptional factors and translocate to the nucleus. Beta- and gamma-catenin are also major substrates for protein tyrosine kinases, and tyrosine phosphorylation of junctional proteins is correlated with decreased adhesiveness. One way in which catenin functions are modulated is by dynamic incorporation into junctional complexes which controls, in part, the cytoplasmic levels of catenins. Here we show that: (1) vascular endothelial growth factor (VEGF) induces beta-catenin tyrosine phosphorylation in a time-, and dose-dependent manner and that VEGF receptors co-localize to areas of endothelial cell-cell contact in vitro and in vivo. (2) Platelet-endothelial cell adhesion molecule (PECAM)-1 can function as a reservoir for, and modulator of, tyrosine phosphorylated beta-catenin. (3) PECAM-1 can prevent beta-catenin nuclear translocation in transfected SW480 colon carcinoma cells. We suggest that PECAM-1 may play a role in modulating beta-catenin tyrosine phosphorylation levels, localization and signaling and by doing so, functions as an important modulator of the endothelium.
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PMID:PECAM-1 (CD31) functions as a reservoir for and a modulator of tyrosine-phosphorylated beta-catenin. 1046 17

The impact of xenobiotics on intercellular adhesion, a fundamental biological process regulating most, if not all, cellular pathways, has been sparsely investigated. Cell-cell adhesion is regulated in the epithelium primarily by the E-cadherin/catenin complex. To characterize the impact of oxidative stress on the E-cadherin/catenin complex, precision-cut mouse liver slices were challenged with two model compounds for the generation of oxidative stress, diamide (DA; 25-250 microM) or t-butylhydroperoxide (tBHP; 5-50 microM), for 6 h. At the concentrations used, neither compound elicited cytotoxicity, as assessed by intracellular K+ content and leakage of lactate dehydrogenase into the culture media. However, a 25% reduction in non-protein sulfhydryl levels, an indication of oxidative perturbation, was seen in liver slices treated with DA or tBHP. Total protein expression of E-cadherin, beta-, or alpha-catenin was not affected by challenge with DA or tBHP. A decrease of beta-catenin in the SDS-soluble fraction of slices, an indicator of the formation of the adhesion complex, was observed. Additionally, a decrease in beta-catenin interactions with E-cadherin and alpha-catenin, as assessed by immunoprecipitation and Western blot analysis, was seen. Disruption of the E-cadherin/catenin complex by tBHP, but not DA, correlated with enhanced tyrosine phosphorylation of beta-catenin. These results suggest that noncytotoxic oxidative stress disrupts the E-cadherin/catenin cell adhesion complex in precision-cut mouse liver slices.
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PMID:Chemically induced oxidative stress disrupts the E-cadherin/catenin cell adhesion complex. 1049 79

Active migration of tumor cells is usually assessed as single cell locomotion in vitro using Boyden chamber-type assays. In vivo, however, carcinoma cells, malignant cells of epithelial origin, frequently invade the surrounding tissue as coherent clusters or nests of cells. We have called this type of movement "cohort migration". In our work, the invasion front of colon carcinomas consisted of compact tumor glands, partially resolved glands or markedly resolved glands with scattered tumor cell clusters or single cells lying ahead. In the former two types, which constituted about a half of all cases, cohort migration seems to be the predominant mechanism, whereas both cohort migration and single cell locomotion may be involved in the last one. In this light, it is very advantageous to investigate the mechanisms involved in the cohort migration. In this review, we present a two-dimensional motility assay as a cohort migration model, in which human colorectal carcinoma cells move outwards from the cell islands mainly as localized coherent sheets of cells when stimulated with 12-O-tetradecanoylphorbol-13-acetate (TPA) or hepatocyte growth factor/scatter factor (HGF/SF). Within the migrating cell sheets, wide intercellular gaps occur at the lower portion of the cells to allow the cells to extend leading lamellae forward while close cell-cell contacts remain at the upper portion of the cells. This localized modulation of cell-cell adhesion at the lower portion of the cells is associated with increased tyrosine phosphorylation of the E-cadherin-catenin complex in TPA-induced cohort migration and with reduced alpha-catenin complexed with E-cadherin in HGF/SF-induced cohort migration. Furthermore, fibronectin deposited by migrating cells is essential for their movement, and on the gelatin-coated substrate even degradation and remodeling of the substrate by matrix metalloproteinases are also needed. Thus, in cohort migration it is likely that cells are released from cell-cell adhesion only at the lower portion of the cells via modulation of E-cadherin-catenin-based mechanism, and this change allows the cells to extend leading lamellae onto the extracellular matrix substrate remodeled by deposition of fibronectin and organized digestion.
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PMID:Cohort migration of carcinoma cells: differentiated colorectal carcinoma cells move as coherent cell clusters or sheets. 1050 35

During mouse preimplantation development, the components of the E-cadherin-catenin complex are derived from both maternal and zygotic gene activity and the adhesion complex is increasingly accumulated and stored in a nonfunctional form, ready to be used for compaction and the formation of the trophectoderm cell layer (Ohsugi et al., Dev. Dyn. 206:391-402, 1996). Here, we show that beta-catenin is a major tyrosine-phosphorylated protein in oocytes and early cleavage-stage embryos and that the relative amount of phosphorylated beta-catenin is greatly reduced during the morula-blastocyst transition. Peptide-specific antibodies indicate that beta-catenin undergoes conformational changes and/or that the carboxy-terminal region of beta-catenin is blocked during preimplantation development. Moreover, the availability of a carboxy-terminal epitope seems to depend on the tyrosine phosphorylation state of beta-catenin and becomes unmasked when oocytes are treated with the tyrosine kinase inhibitor genistein. Our results suggest that tyrosine phosphorylation of beta-catenin represents a molecular mechanism to keep the accumulating E-cadherin adhesion complex in a nonfunctional form. Dev Dyn 1999;216:168-176.
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PMID:Beta-catenin is a major tyrosine-phosphorylated protein during mouse oocyte maturation and preimplantation development. 1053 56

Alteration of cadherin-mediated cell-cell adhesion is frequently associated to tyrosine phosphorylation of p120- and beta-catenins. We have examined the role of this modification in these proteins in the control of beta-catenin/E-cadherin binding using in vitro assays with recombinant proteins. Recombinant pp60(c-src) efficiently phosphorylated both catenins in vitro, with stoichiometries of 1.5 and 2.0 mol of phosphate/mol of protein for beta-catenin and p120-catenin, respectively. pp60(c-src) phosphorylation had opposing effects on the affinities of beta-catenin and p120 for the cytosolic domain of E-cadherin; it decreased (in the case of beta-catenin) or increased (for p120) catenin/E-cadherin binding. However, a role for p120-catenin in the modulation of beta-catenin/E-cadherin binding was not observed, since addition of phosphorylated p120-catenin did not modify the affinity of phosphorylated (or unphosphorylated) beta-catenin for E-cadherin. The phosphorylated Tyr residues were identified as Tyr-86 and Tyr-654. Experiments using point mutants in these two residues indicated that, although Tyr-86 was a better substrate for pp60(c-src), only modification of Tyr-654 was relevant for the interaction with E-cadherin. Transient transfections of different mutants demonstrated that Tyr-654 is phosphorylated in conditions in which adherens junctions are disrupted and evidenced that binding of beta-catenin to E-cadherin in vivo is controlled by phosphorylation of beta-catenin Tyr-654.
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PMID:Regulation of E-cadherin/Catenin association by tyrosine phosphorylation. 1059 80

Thrombin-mediated changes in endothelial cell adherens junctions modulate vascular permeability. We demonstrate that the nonreceptor protein-tyrosine phosphatase SHP2 co-precipitates with VE-cadherin complexes in confluent, quiescent human umbilical vein endothelial cells. Ligand-binding blots using a SHP2-glutathione S-transferase fusion peptide established that SHP2 associates selectively with beta-catenin in VE-cadherin complexes. Thrombin treatment of human umbilical vein endothelial cells promotes SHP2 tyrosine phosphorylation and dissociation from VE-cadherin complexes. The loss of SHP2 from the cadherin complexes correlates with a dramatic increase in the tyrosine phosphorylation of beta-catenin, gamma-catenin, and p120-catenin complexed with VE-cadherin. We propose that thrombin regulates the tyrosine phosphorylation of VE-cadherin-associated beta-catenin, gamma-catenin, and p120-catenin by modulating the quantity of SHP2 associated with VE-cadherin complexes. Such changes in adherens junction complex composition likely underlie thrombin-elicited alterations in endothelial monolayer permeability.
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PMID:SHP2 association with VE-cadherin complexes in human endothelial cells is regulated by thrombin. 1068 92


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