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

The Armadillo family is formed by proteins which possess an Arm domain comprising multiple copies of a 42-amino-acid motif, the Arm repeat, initially described for the Drosophila segment polarity gene product Armadillo. The Arm domain serves in protein-protein interactions which are required for the family members Armadillo, beta-catenin and plakoglobin to mediate cell-cell adhesion and Wnt/Wingless signalling. Similarily, p120cas, the Arm domain containing src substrate, also binds to cadherins and becomes tyrosine phosphorylated in response to a variety of stimuli. However, a putative function of p120cas in adhesion or signalling has not yet been demonstrated. It has also not been shown until now that an Arm domain is a common signal transduction motif. Using Xenopus embryos we show by expression of murine p120cas1B (mp120cas1B) in ventral blastomeres that this catenin cannot replace beta-catenin function in dorsal axis formation. Thus, the presence of an Arm domain per se is not sufficient to activate the Wnt/Wg pathway. Indeed, injection of mp120cas1B into dorsal blastomeres led instead to delayed blastopore closure and posteriorized phenotypes with malformed head structures indicative of disturbed gastrulation movements. Because neither convergent extension behaviour nor adhesion to fibronectin was altered in the injected embryos we assume that mp120cas1B influences motility or orientation of migrating mesodermal cells.
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PMID:Expression of the Armadillo family member p120cas1B in Xenopus embryos affects head differentiation but not axis formation. 951 May 42

Alterations in the expression or function of molecules that affect cellular adhesion and proliferation are thought to be critical events for tumor progression. Loss of expression of the cell adhesion molecule E-cadherin and increased expression of the epidermal growth factor receptor are two prominent molecular events that are associated with tumorigenesis. The regulation of E-cadherin-dependent cell adhesion by epidermal growth factor (EGF) was therefore examined in the human breast cancer cell line, MDA-MB-468. In this study, changes were observed in the subcellular distribution of components that mediate the cytoplasmic connection between E-cadherin and the actin-based cytoskeleton in response to activation of the EGF receptor. Serum withdrawal activated E-cadherin-dependent cell-cell aggregation in MDA-MB-468 cells, and this treatment stimulated the interaction of actin, alpha-actinin, and vinculin with E-cadherin complexes, despite the absence of alpha-catenin in these cells. By contrast, the co-precipitation of actin with E-cadherin was not detected in several alpha-catenin positive epithelial cell lines. Treatment with EGF inhibited cellular aggregation but did not affect either the levels of E-cadherin or catenin expression nor the association of catenins (beta-catenin, plakoglobin/gamma-catenin, or p120(cas)) with E-cadherin. However, EGF treatment of the MDA-MB-468 cell line dissociated actin, alpha-actinin, and vinculin from the E-cadherin-catenin complex, and this coincided with a robust phosphorylation of beta-catenin, plakoglobin/gamma-catenin, and p120(cas) on tyrosine residues. Furthermore, inactivation of the EGF receptor in serum-treated MDA-MB-468 cells with either a function-blocking antibody or EGF receptor kinase inhibitors mimicked the effects of serum starvation by stimulating both cellular aggregation and assembly of E-cadherin complexes with vinculin and actin. These results demonstrate that the EGF receptor directly regulates cell-cell adhesion through modulation of the interaction of E-cadherin with the actin cytoskeleton and thus substantiates the coordinate role of both of these molecules in tumor progression and metastasis.
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PMID:The epidermal growth factor receptor modulates the interaction of E-cadherin with the actin cytoskeleton. 953 96

The influence of plakoglobin on the phenotype and tumorigenicity of murine spindle carcinoma cells was analyzed by stable transfection of plakoglobin cDNA in the presence or absence of E-cadherin expression. In either situation, overexpression of plakoglobin was unable to modify the fibroblastic phenotype or to completely suppress the tumorigenic behavior of the spindle cells, but a moderate reduction in the growth rate of the tumors was induced by plakoglobin and was further enhanced by E-cadherin. Coexpression of E-cadherin and plakoglobin induced a mutual stabilization, increasing the half-life of both molecules in the double transfectants more than 5- and 30-fold, respectively, with a turnover rate similar to that observed in control keratinocytes. The stabilization of E-cadherin, as well as that of plakoglobin, was maintained in the tumors induced by the double transfectants, in contrast to the unstable expression of E-cadherin observed in tumors induced in plakoglobin-deficient cells. The E-cadherin/catenin complexes present in the double transfectants were functional in calcium-dependent aggregation assays and similar in composition to those of control keratinocytes. However, most of the components of the complexes of the transfectants were solubilized by non-ionic detergents, indicating a weak interaction with the actin cytoskeleton. These results indicated that restoration of E-cadherin/catenin complexes was not sufficient to induce the transition of the fibroblastic cells to an epithelial phenotype or to completely suppress the tumorigenicity of mouse skin spindle carcinoma cells.
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PMID:Induction of mutual stabilization and retardation of tumor growth by coexpression of plakoglobin and E-cadherin in mouse skin spindle carcinoma cells. 958 57

This report describes the generation and characterization of a panel of monoclonal antibodies (MAb) to the catenin p120ctn. p120ctn (formerly p120cas) is a cadherin-binding protein with structural similarity to the classical catenins beta-catenin and plakoglobin. It was originally identified as a prominent Src substrate and subsequently as a substrate for the Platelet Derived Growth Factor (PDGF), Epidermal Growth Factor (EGF), and Colony Stimulating Factor-1 (CSF-1) receptor tyrosine kinases. To facilitate further study of p120 function, we have generated novel MAbs to both the N- and C-terminal ends of p120 and compared them to previously described antibodies to these regions.
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PMID:Production and characterization of monoclonal antibodies to the catenin p120ctn. 962 58

Cadherins are Ca2+-dependent cell-cell adhesion molecules, and are involved in the formation and maintenance of the histo-architecture. Using a combination of biochemical and immunohistochemical methods, we analyzed the expression of the cadherin-catenin complex in 34 human hepatocellular carcinomas. Unexpectedly, we found the expression of N (neural)-cadherin in normal hepatocytes and all hepatocellular carcinomas examined. In 18 cases, the decreased expression of E (epithelial)-cadherin was observed. Among them, the decreased expression of alpha-catenin and gamma-catenin (plakoglobin) was also observed in 9 and 6 cases, respectively. Thus the decreased expression of alpha-catenin and gamma-catenin was apparently preceded by the decreased expression of E-cadherin. The decreased expression of beta-catenin was not observed in any of the cases analyzed. beta-Catenin was found to accumulate in the cytoplasm of hepatocellular carcinomas with the decreased expression of E-cadherin, despite the presence of N-cadherin at the cell-cell contacts. These results suggest a pivotal role of E-cadherin in the intracellular distribution of catenins in hepatocellular carcinomas.
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PMID:E-cadherin but not N-cadherin expression is correlated with the intracellular distribution of catenins in human hepatocellular carcinomas. 968 18

We examined intercadherin interactions in epithelial A-431 cells producing endogenous E-cadherin and recombinant forms of E-cadherin tagged either by myc or by flag epitopes. Three distinct E-cadherin complexes were found. The first is a conventional E-cadherin-catenin complex consisting of one E-cadherin molecule linked either to beta-catenin/alpha-catenin or to plakoglobin/alpha-catenin dimers. The second is a lateral E-cadherin complex incorporating two E-cadherin- catenin conventional complexes combined in parallel fashion via dimerization of the NH2-terminal extracellular domain of E-cadherin. The third complex is likely to contain two E-cadherin-catenin conventional complexes derived from two opposing cells and arranged in an antiparallel fashion. Formation of the antiparallel but not lateral complex strictly depends on extracellular calcium and E-cadherin binding to catenins. Double amino acid substitution Trp156Ala/Val157Gly within the extracellular NH2-terminal E-cadherin domain completely abolished both lateral and antiparallel inter-E-cadherin association. These data support an idea that the antiparallel complex has the adhesion function. Furthermore, they allow us to suggest that antiparallel complexes derive from lateral dimers and this complex process requires catenins and calcium ions.
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PMID:Adhesive but not lateral E-cadherin complexes require calcium and catenins for their formation. 970 Jan 70

Vascular endothelial cells assemble adhesive intercellular junctions comprising a unique cadherin, VE-cadherin, which is coupled to the actin cytoskeleton through cytoplasmic interactions with plakoglobin, beta-catenin and alpha -catenin. However, the potential linkage between VE-cadherin and the vimentin intermediate filament cytoskeleton is not well characterized. Recent evidence indicates that lymphatic and vascular endothelial cells express desmoplakin, a cytoplasmic desmosomal protein that attaches intermediate filaments to the plasma membrane in epithelial cells. In the present study, desmoplakin was localized to intercellular junctions in human dermal microvascular endothelial cells. To determine if VE-cadherin could associate with desmoplakin, VE-cadherin, plakoglobin, and a desmoplakin amino-terminal polypeptide (DP-NTP) were co-expressed in L-cell fibroblasts. In the presence of VE-cadherin, both plakoglobin and DP-NTP were recruited to cell-cell borders. Interestingly, beta-catenin could not substitute for plakoglobin in the recruitment of DP-NTP to cell borders, and DP-NTP bound to plakoglobin but not beta-catenin in the yeast two-hybrid system. In addition, DP-NTP colocalized at cell-cell borders with alpha-catenin in the L-cell lines, and endogenous desmoplakin and alpha-catenin colocalized in cultured dermal microvascular endothelial cells. This is in striking contrast to epithelial cells, where desmoplakin and alpha -+catenin are restricted to desmosomes and adherens junctions, respectively. These results suggest that endothelial cells assemble unique junctional complexes that couple VE-cadherin to both the actin and intermediate filament cytoskeleton.
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PMID:VE-cadherin and desmoplakin are assembled into dermal microvascular endothelial intercellular junctions: a pivotal role for plakoglobin in the recruitment of desmoplakin to intercellular junctions. 973 78

The cadherin/catenin complexes expressed by a murine epidermal keratinocyte cell line PDV, expressing E- and P-cadherin, have been analysed using a combination of biochemical and confocal microscopy analysis. Two types of E-cadherin complexes, containing beta-catenin or plakoglobin and alpha-catenin, were detected in PDV cells as in other cell types, while P-cadherin was mainly detected in complexes containing beta-catenin and alpha-catenin in PDV and other murine epidermal keratinocytes. Biotin-labelling studies have shown that both types of E-cadherin complexes are present at the surface of confluent cells. Furthermore, confocal microscopy analysis indicated that E-cadherin/plakoglobin complexes are located in stable cell-cell contacts at the middle lateral membranes and associated with alpha-catenin and the actin cytoskeleton, with a similar distribution to that to the E-cadherin/beta-catenin complexes. In addition, E-cadherin/plakoglobin complexes not associated with alpha-catenin or the actin cytoskeleton were detected in lower planes of the lateral contacting membranes as well as E-cadherin non-associated with catenins in the more basal planes. These studies support that in murine epidermal keratinocytes both beta-catenin- and plakoglobin-containing E-cadherin complexes contribute to the maintenance of stable cell-cell contacts and suggest a differential role of the plakoglobin containing complexes in different epithelial cell types.
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PMID:Cadherin/catenin complexes in murine epidermal keratinocytes: E-cadherin complexes containing either beta-catenin or plakoglobin contribute to stable cell-cell contacts. 975 21

Cadherin mediated cell-cell adhesion requires cytoplasmic connections to the cytoskeleton mediated by alpha-catenin. Original descriptions of the catenins, as well as our own in vitro studies, have suggested that this connection was mediated by the interaction of alpha-catenin to actin. Loss of adhesion in the human colon carcinoma cell line "Clone A" is the result of an internal deletion mutation of 158 residues near the N-terminus of the protein resulting in an 80 kD mutated protein. Transfection of these cells with the full length protein restores the normal adhesive phenotype. We have characterized this mutant protein in efforts to understand the normal function of alpha-catenin and, in particular, the region deleted in the Clone A mutant. Co-precipitation experiments using whole cell lysates indicate that the mutant form of alpha-catenin binds beta-catenin and plakoglobin, and can form a structural complex with E-cadherin via these interactions. Actin co-sedimentation assays show that the recombinant mutant binds and bundles F-actin and binds both actin and beta-catenin simultaneously, as seen with wild type alpha-catenin. These results suggest that the stabilization of the E-cadherin-catenin complex may be mediated by factors beyond its direct interaction with actin. We conclude that a region near the N-terminus of alpha-catenin mediates additional interactions between the adhesive complex and the cytoskeleton that are critical for functional adhesion.
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PMID:A mutation in alpha-catenin disrupts adhesion in clone A cells without perturbing its actin and beta-catenin binding activity. 976 69

One of the hallmarks of polarized epithelial cells undergoing mitosis is their rounded morphology. This phenotype correlates with a reduced cell-substratum adhesion, apparently caused by a modulation of integrin function. However, it is still unclear whether the cadherin-mediated cell-cell adhesion is affected as well. To address this question, the cadherin complex was analyzed in different cell cycle stages of Madin-Darby canine kidney cells. By immunofluorescence, mitotic Madin-Darby canine kidney cells showed an increased staining of E-cadherin and the catenins (alpha-catenin, beta-catenin, plakoglobin, p120(ctn)) in the cytosol, suggesting a reorganization of the cadherin-catenin complex during mitosis. Biochemical analysis revealed that the overall amount of these components, as well as the proportion of the complex associated with the actin cytoskeleton, remained unchanged in mitotic cells. However, we found evidence for an internalization of E-cadherin during mitosis. In addition, the cadherin-catenin complex was analyzed for mitosis-specific changes in phosphorylation. We report a decrease in the tyrosine phosphorylation of beta-catenin, plakoglobin, and p120(ctn) during mitosis. Moreover, we observed a mitosis-specific Ser/Thr-phosphorylation of p120(ctn), as detected by the MPM-2 antibody. Hence, the cadherin/catenin complex is a target for different posttranslational modifications during mitosis, which may also have a profound impact on cadherin-mediated cell-cell adhesion.
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PMID:Modification of the E-cadherin-catenin complex in mitotic Madin-Darby canine kidney epithelial cells. 977 55


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