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)

Cadherins are calcium-dependent, cell surface glycoproteins involved in cell-cell adhesion. To function in cell-cell adhesion, the transmembrane cadherin molecule must be associated with the cytoskeleton via cytoplasmic proteins known as catenins. Three catenins, alpha-catenin, beta-catenin and gamma-catenin (also known as plakoglobin), have been identified. beta-catenin or plakoglobin is associated directly with the cadherin; alpha-catenin binds to beta-catenin/plakoglobin and serves to link the cadherin/catenin complex to the actin cytoskeleton. The domains on the cadherin and betacatenin/plakoglobin that are responsible for protein-protein interactions have been mapped. However, little is known about the molecular interactions between alpha-catenin and beta-catenin/plakoglobin or about the interactions between alpha-catenin and the cytoskeleton. In this study we have used the yeast two-hybrid system to map the domains on alpha-catenin that allow it to associate with beta-catenin/plakoglobin and with alpha-actinin. We also identify a region on alpha-actinin that is responsible for its interaction with alpha-catenin. The yeast two-hybrid data were confirmed with biochemical studies.
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PMID:Characterization of the interactions of alpha-catenin with alpha-actinin and beta-catenin/plakoglobin. 915 27

During early heart development the expression pattern of N-cadherin, a calcium-dependent cell adhesion molecule, suggests its involvement in morphoregulation and the stabilization of cardiomyocyte differentiation. N-cadherin's adhesive activity is dependent upon its interaction with the intracellular catenins. An association with alpha-catenin and beta-catenin also is believed to be involved in cell signaling. This study details the expression patterns of alpha-catenin, beta-catenin, and gamma-catenin, during definition of the cardiac cell population as distinct compartments in the anterior regions of the chick embryo between stages 5 and 9. The restriction of N-cadherin/catenin localization at stage 5+ from a uniform pattern in vivo, to specific cell clusters that demarcate areas where mesoderm separation is initiated, suggests that the N-cadherin/catenin complex is involved in boundary formation and in the subsequent cell sorting. The latter two processes lead to the specification and formation of the somatic and cardiac splanchnic mesoderm. N-cadherin colocalized with alpha- and beta-catenin at the cell membrane before and during the time that its expression becomes restricted to the lateral mesoderm and continues cephalocaudad into stage 8. These proteins continue to colocalize in the myocardium of the tubular heart. Plakoglobin is not expressed in this region during stages 6-8, but is detected in the myocardium later at stage 13. The observed in vivo expression patterns of alpha-catenin, beta-catenin, and plakoglobin suggest that these proteins are directly linked with the developmental regulation of cell junctions, as cardiac cells become stably committed and phenotypically differentiated to eventually form a mature myocardium. The localization of N-CAM also was analyzed during these stages to determine whether the N-cadherin-catenin localization was unique or whether other cell adhesion molecules were expressed similarly. The results indicate that the unique pattern of N-cadherin expression is not shared with N-CAM. We also show that perturbation of N-cadherin using a function perturbing N-cadherin antibody (NCD-2) inhibits normal early heart development and myogenesis in a cephalocaudad, stage-dependent manner. We propose a model whereby myocardial cell compartmentalization also defines the endocardial population. The presence of beta-catenin suggests that a similar signaling pathway involving Wnt (wingless)-mediated events may function in myocardial cell compartmentalization during early vertebrate heart development, as in Drosophila contractile vessel development.
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PMID:N-cadherin-catenin interaction: necessary component of cardiac cell compartmentalization during early vertebrate heart development. 918 80

Trophectoderm epithelium formation, the first visible differentiation process during mouse embryonic development, is affected in embryos lacking the cell adhesion molecule E-cadherin. Here we analyze the developmental potential of such E-cadherin-negative embryos, focusing on the organization of cell junctions and the cytoskeleton. To do this we used antibodies directed against alpha-, beta-, or gamma-(plakoglobin)-catenin and junctional and cytoskeletal proteins including ZO-1 and occludin (tight junctions), desmoglein1 (desmosomes), connexin43 (gap junctions), and EndoA (cytokeratin intermediate filaments). Membrane localization of alpha- and beta-catenin, and ZO-1, as well as cortical actin filament organization were abnormal in E-cadherin-negative embryos, and the expression levels of alpha- and beta-catenin were dramatically reduced, all suggesting a regulatory role for E-cadherin in forming the cadherin-catenin complex. In contrast, the membrane localization of plakoglobin, occludin, desmoglein1, connexin43, and cytokeratin filaments appeared unaltered. The unusual morphogenesis in E-cadherin-negative embryos apparently reflects defects in the molecular architecture of a supermolecular assembly involving zonulae adherens, tight junctions, and cortical actin filament organization, although the individual structures still appeared normal in electron microscopical analysis.
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PMID:Cell-junctional and cytoskeletal organization in mouse blastocysts lacking E-cadherin. 918 87

Most receptor-like protein tyrosine phosphatases (PTPases) display a high degree of homology with cell adhesion molecules in their extracellular domains. We studied the functional significance of processing for the receptor-like PTPases LAR and PTPsigma. PTPsigma biosynthesis and intracellular processing resembled that of the related PTPase LAR and was expressed on the cell surface as a two-subunit complex. Both LAR and PTPsigma underwent further proteolytical processing upon treatment of cells with either calcium ionophore A23187 or phorbol ester TPA. Induction of LAR processing by TPA in 293 cells did require overexpression of PKCalpha. Induced proteolysis resulted in shedding of the extracellular domains of both PTPases. This was in agreement with the identification of a specific PTPsigma cleavage site between amino acids Pro821 and Ile822. Confocal microscopy studies identified adherens junctions and desmosomes as the preferential subcellular localization for both PTPases matching that of plakoglobin. Consistent with this observation, we found direct association of plakoglobin and beta-catenin with the intracellular domain of LAR in vitro. Taken together, these data suggested an involvement of LAR and PTPsigma in the regulation of cell contacts in concert with cell adhesion molecules of the cadherin/catenin family. After processing and shedding of the extracellular domain, the catalytically active intracellular portions of both PTPases were internalized and redistributed away from the sites of cell-cell contact, suggesting a mechanism that regulates the activity and target specificity of these PTPases. Calcium withdrawal, which led to cell contact disruption, also resulted in internalization but was not associated with prior proteolytic cleavage and shedding of the extracellular domain. We conclude that the subcellular localization of LAR and PTPsigma is regulated by at least two independent mechanisms, one of which requires the presence of their extracellular domains and one of which involves the presence of intact cell-cell contacts.
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PMID:Cellular redistribution of protein tyrosine phosphatases LAR and PTPsigma by inducible proteolytic processing. 924 95

The E-cadherin-catenin adhesion complex has been the subject of many structural and functional studies because of its importance in development, normal tissue function and carcinogenesis. It is well established that the cytoplasmic domain of E-cadherin binds either beta-catenin or plakoglobin, which both can assemble alpha-catenin into the complex. Recently we have identified an alpha-catenin binding site in beta-catenin and plakoglobin and postulated, based on sequence analysis, that these protein-protein interactions are mediated by a hydrophobic interaction mechanism. Here we have now identified the reciprocal complementary binding site in alpha-catenin which mediates its interaction with beta-catenin and plakoglobin. Using in vitro association assays with C-terminal truncations of alpha-catenin expressed as recombinant fusion proteins, we found that the N-terminal 146 amino acids are required for this interaction. We then identified a peptide of 27 amino acids within this sequence (amino acid positions 117-143) which is necessary and sufficient to bind beta-catenin or plakoglobin. As shown by mutational analysis, hydrophobic amino acids within this binding site are important for the interaction. The results described here, together with our previous work, give strong support for the idea that these proteins associate by hydrophobic interactions of two alpha-helices.
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PMID:A specific domain in alpha-catenin mediates binding to beta-catenin or plakoglobin. 926 63

It has been recently proposed that adhesion of polymorphonuclear cells (PMNs) to human umbilical vein endothelial cells leads to the disorganization of the vascular endothelial cadherin-dependent endothelial adherens junctions. Combined immunofluorescence and biochemical data suggested that after adhesion of PMNs to the endothelial cell surface, beta-catenin, as well as plakoglobin was lost from the cadherin/catenin complex and from total cell lysates. In this study we present data that strongly suggest that the adhesion-dependent disappearance of endothelial catenins is not mediated by a leukocyte to endothelium signaling event, but is due to the activity of a neutrophil protease that is released upon detergent lysis of the cells.
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PMID:In vitro degradation of endothelial catenins by a neutrophil protease. 944 15

Cell-cell adhesion mediated by E-cadherin is often lost or disturbed in human carcinomas. For regular adhesive function, E-cadherin has to form complexes with peripheral cytoplasmic catenins which are multifunctional proteins that are also involved in signal transduction and growth regulation. We have analyzed the expression levels of the genes encoding alpha-catenin, beta-catenin and plakoglobin in correlation to the E-cadherin expression levels in cell lines derived from human cervical carcinomas. Reduced mRNA and protein levels were detected for plakoglobin, whereas alpha- and beta-catenin showed only reduced protein (but not mRNA) levels. The alterations in catenin gene expression were often associated with absent or reduced E-cadherin. The findings indicate that a reduction of catenin gene expression may contribute to the development of cervical carcinomas.
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PMID:Reduced gene expression of E-cadherin and associated catenins in human cervical carcinoma cell lines. 946 Oct 36

Angiogenesis plays an important role in various diseases and conditions such as malignant tumor, wound healing, and atherosclerosis. Since cell-to-cell adhesion may play a key role in angiogenesis, we investigated the effect of the cadherin-catenin-cytoskeleton complex on angiogenesis in human umbilical vein endothelial cells (HUVECs). Immunofluorescence staining revealed that alpha-catenin, beta-catenin, and plakoglobin were concentrated at cell-cell contacts in HUVECs. Antisense oligonucleotide (AS-oligo), complementary to the region of human plakoglobin was dissolved in saline and applied to the media at 1 mM every 12 h for 4 days, and sense oligonucleotide (S-oligo) was used as control. HUVEC migration from an injury line was enhanced by AS-oligo. Interestingly, HUVECs migrated in line with S-oligo, and in a scattered fashion with AS-oligo. Tube formation on Matrigel occurred earlier with AS-oligo than with S-oligo. These findings indicate that plakoglobin inhibited HUVEC migration and tube formation (angiogenesis) by regulating cell-cell adhesion.
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PMID:The role of cadherin-catenin-cytoskeleton complex in angiogenesis: antisense oligonucleotide of plakoglobin promotes angiogenesis in vitro, and protein kinase C (PKC) enhances angiogenesis through the plakoglobin signaling pathway. 947 58

Leukemia cells (K562) that grow as non-adhesive single cells and have no endogenous cadherin were transfected with an E-cadherin expression vector, and cell clones stably expressing E-cadherin on their surface were established. The expression of E-cadherin induced the up-regulation of catenins, and E-cadherin became associated with catenins. The transfected cells grew as floating aggregates. Cell aggregation was Ca2+-dependent and was inhibited by E-cadherin antibodies. The aggregates dissociated into single cells on the addition of pervanadate. Pervanadate caused a dramatic augmentation of the phosphorylation of E-cadherin, beta-catenin, and gamma-catenin (plakoglobin), but alpha-catenin was not detectably phosphorylated. After pervanadate treatment, beta-catenin and gamma-catenin migrated more slowly on gel electrophoresis, suggesting changes in their conformations due to eventual changes in their phosphorylation levels. In the treated cells, a significant amount of alpha-catenin was dissociated from the E-cadherin.catenin complex. Aggregates of cells expressing an E-cadherin chimeric molecule covalently linked with alpha-catenin were not dissociated on pervanadate treatment, supporting the idea that the dissociation of alpha-catenin from the complex underlies the observed E-cadherin dysfunction.
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PMID:Altered cell adhesion activity by pervanadate due to the dissociation of alpha-catenin from the E-cadherin.catenin complex. 949 37

The two major cadherins of endothelial cells are neural (N)-cadherin and vascular endothelial (VE)- cadherin. Despite similar level of protein expression only VE-cadherin is located at cell-cell contacts, whereas N-cadherin is distributed over the whole cell membrane. Cotransfection of VE-cadherin and N-cadherin in CHO cells resulted in the same distribution as that observed in endothelial cells indicating that the behavior of the two cadherins was not cell specific but related to their structural characteristics. Similar amounts of alpha- and beta-catenins and plakoglobin were associated to VE- and N-cadherins, whereas p120 was higher in the VE-cadherin complex. The presence of VE-cadherin did not affect N-cadherin homotypic adhesive properties or its capacity to localize at junctions when cotransfectants were cocultured with cells transfected with N-cadherin only. To define the molecular domain responsible for the VE-cadherin-dominant activity we prepared a chimeric construct formed by VE-cadherin extracellular region linked to N-cadherin intracellular domain. The chimera lost the capacity to exclude N-cadherin from junctions indicating that the extracellular domain of VE-cadherin alone is not sufficient for the preferential localization of the molecule at the junctions. A truncated mutant of VE-cadherin retaining the full extracellular domain and a short cytoplasmic tail (Arg621-Pro702) lacking the catenin-binding region was able to exclude N-cadherin from junctions. This indicates that the Arg621-Pro702 sequence in the VE-cadherin cytoplasmic tail is required for N-cadherin exclusion from junctions. Competition between cadherins for their clustering at intercellular junctions in the same cell has never been described before. We speculate that, in the endothelium, VE- and N-cadherin play different roles; whereas VE-cadherin mostly promotes the homotypic interaction between endothelial cells, N-cadherin may be responsible for the anchorage of the endothelium to other surrounding cell types expressing N-cadherin such as vascular smooth muscle cells or pericytes.
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PMID:Differential localization of VE- and N-cadherins in human endothelial cells: VE-cadherin competes with N-cadherin for junctional localization. 950 79


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