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 cytoplasmic region of the Ca(2+)-dependent cell-adhesion molecule (CAM) uvomorulin associates with distinct cytoplasmic proteins with molecular masses of 102, 88, and 80 kDa termed alpha, beta, and gamma catenin, respectively. This complex formation links uvomorulin to the actin filament network, which seems to be of primary importance for its cell-adhesion properties. We show here that antibodies against alpha catenin also immunoprecipitate complexes that contain human N-cadherin, mouse P-cadherin, chicken A-CAM (adherens junction-specific CAM; also called N-cadherin) or Xenopus U-cadherin, demonstrating that alpha catenin is complexed with other cadherins. In immunofluorescence tests, alpha catenin is colocalized with cadherins at the plasma membrane. However, in cadherin-negative Ltk- cells, alpha catenin is found uniformly distributed in the cytoplasm, suggesting some additional biological function(s). Expression of uvomorulin in these cells results in a concentration of alpha catenin at membrane areas of cell contacts. We also have cloned and sequenced murine alpha catenin. The deduced amino acid sequence reveals a significant homology to vinculin. Our results suggest the possibility of a new vinculin-related protein family involved in the cytoplasmic anchorage of cell-cell and cell-substrate adhesion molecules.
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PMID:The uvomorulin-anchorage protein alpha catenin is a vinculin homologue. 192 79

Calcium-dependent homotypic cell-cell adhesion, mediated by molecules such as E-cadherin, guides the establishment of classical epithelial cell polarity and contributes to the control of migration, growth, and differentiation. These actions involve additional proteins, including alpha- and beta-catenin (or plakoglobin) and p120, as well as linkage to the cortical actin cytoskeleton. The molecular basis for these interactions and their hierarchy of interaction remain controversial. We demonstrate a direct interaction between F-actin and alpha (E)-catenin, an activity not shared by either the cytoplasmic domain of E-cadherin or beta-catenin. Sedimentation assays and direct visualization by transmission electron microscopy reveal that alpha 1(E)-catenin binds and bundles F-actin in vitro with micromolar affinity at a catenin/G-actin monomer ratio of approximately 1:7 (mol/mol). Recombinant human beta-catenin can simultaneously bind to the alpha-catenin/actin complex but does not bind actin directly. Recombinant fragments encompassing the amino-terminal 228 residues of alpha 1(E)-catenin or the carboxyl-terminal 447 residues individually bind actin in cosedimentation assays with reduced affinity compared with the full-length protein, and neither fragment bundles actin. Except for similarities to vinculin, neither region contains sequences homologous to established actin-binding proteins. Collectively these data indicate that alpha 1 (E)-catenin is a novel actin-binding and -bundling protein and support a model in which alpha 1(E)-catenin is responsible for organizing and tethering actin filaments at the zones of E-cadherin-mediated cell-cell contact.
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PMID:Alpha 1(E)-catenin is an actin-binding and -bundling protein mediating the attachment of F-actin to the membrane adhesion complex. 756 23

Adherens-type junctions (AJ) are specialized intercellular contacts, mediated by cadherins and characterized by the association with actin filaments through a vinculin- and catenin-rich submembrane plaque. We describe here two mechanisms which potentiate AJ formation in mesenchymal cells. These include the augmentation of AJ by the co-expression of another adhesion molecule, namely NCAM, and the stimulation of tyrosine phosphorylation. These effects were obtained in NIH-3T3 cells, which, under normal conditions, have poor cadherin- and vinculin-containing intercellular junctions. The transfection of these cells with cDNA encoding the 140kD NCAM resulted in the extensive formation of cadherin- and vinculin-rich AJ, demonstrating a cooperativity between the two junctional systems. AJ could also be induced in 3T3, and in CEF and COS cells, upon a brief exposure to H2O2/vanadate, which elevates cellular levels of phosphotyrosine due to inhibition of tyrosine-specific phosphatases. This induction was, however, transient since prolonged exposure to H2O2/vanadate resulted in an overall destruction of AJ and detachment of cells from each other and from the extracellular matrix. AJ formation appears, therefore, to be modulated by a variety of factors including the level of expression of its intrinsic components, the cooperative effect of other adhesion molecules, and by tyrosine-phosphorylation.
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PMID:Augmentation of adherens junction formation in mesenchymal cells by co-expression of N-CAM or short-term stimulation of tyrosine-phosphorylation. 774 36

Cadherins are Ca(2+)-dependent, cell surface glycoproteins involved in cell-cell adhesion. Extracellularly, transmembrane cadherins such as E-, P-, and N-cadherin self-associate, while intracellularly they interact indirectly with the actin-based cytoskeleton. Several intracellular proteins termed catenins, including alpha-catenin, beta-catenin, and plakoglobin, are tightly associated with these cadherins and serve to link them to the cytoskeleton. Here, we present evidence that in fibroblasts alpha-actinin, but not vinculin, colocalizes extensively with the N-cadherin/catenin complex. This is in contrast to epithelial cells where both cytoskeletal proteins colocalize extensively with E-cadherin and catenins. We further show that alpha-actinin, but not vinculin, coimmunoprecipitates specifically with alpha- and beta-catenin from N- and E-cadherin-expressing cells, but only if alpha-catenin is present. Moreover, we show that alpha-actinin coimmunoprecipitates with the N-cadherin/catenin complex in an actin-independent manner. We therefore propose that cadherin/catenin complexes are linked to the actin cytoskeleton via a direct association between alpha-actinin and alpha-catenin.
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PMID:Interaction of alpha-actinin with the cadherin/catenin cell-cell adhesion complex via alpha-catenin. 779 Mar 78

At least three proteins (alpha, beta, and gamma catenin) comprise the cytoplasmic domain of the cadherin cell-cell adhesion complex. We have cloned and sequenced human epithelial alpha(E)-catenin and have identified two distinct transcripts, designated alpha 1- and alpha 2-. The human alpha 1(E)-catenin transcript predicts a 907 aa sequence 97% identical to mouse alpha-catenin. The second transcript, alpha 2(E)-catenin, displays a 24 amino acid insertion after codon 812, yielding a 931 amino acid protein (GenBank #L23805). Analysis by RT-PCR and Northern blotting detects one or both transcripts in epithelial and non-epithelial tissues. Southern blotting indicates that both arise from a single gene. The alternative transcription site in alpha-catenin is analogous to the splice site in vinculin that creates met alpha-vinculin, extending the homology between alpha-catenin and vinculin. These data with the reported structure of other catenin genes suggest that vinculin and alpha-catenin generate a superfamily of proteins mediating membrane-cytoskeletal associations.
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PMID:Molecular cloning reveals alternative splice forms of human alpha(E)-catenin. 794 18

Catenins are peripheral cytoplasmic proteins originally identified in association with the mouse epithelial cell adhesion molecule E-cadherin. Molecular cloning and primary structure analysis demonstrated that alpha-catenin is homologous to vinculin and the beta-catenin is homologous to human plakoglobin and the Drosophila gene product armadillo. With the use of peptide-specific anti plakoglobin antibodies were confirm here that plakoglobin is a component of the cadherin-catenin complex and that it is most likely identical to gamma-catenin. We show that plakoglobin binds directly to E-cadherin. We consolidate the biochemical evidence for the existence of two distinct and separable E-cadherin-catenin complexes in the same cell. One complex is composed of E-cadherin, alpha- and beta-catenin, the other of E-cadherin, alpha-catenin and plakoglobin. A similar distinct association with catenins is also found for other cadherins. Comparison of different cell lines revealed that the relative amounts of the two complexes vary depending on cell types.
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PMID:Distinct cadherin-catenin complexes in Ca(2+)-dependent cell-cell adhesion. 798

Cadherins are a family of transmembrane glycoproteins which are responsible for calcium-dependent cell-cell adhesion. At least two types of proteins called alpha- and beta-catenin are known to be closely associated with the cytoplasmic domain of cadherin molecules and to play a crucial role in the regulation of cadherin cell adhesion function. Sequence analyses of cDNAs encoding these catenins have revealed that alpha- and beta-catenins have a similarity to vinculin and Drosophila armadillo protein, respectively. The possible involvement of these catenin molecules in the molecular mechanism of human cancer invasion and metastasis is discussed.
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PMID:[Regulation of cadherin-based cell adhesion and metastasis]. 843 80

The elevation of tyrosine phosphorylation level is thought to induce the dysfunction of cadherin through the tyrosine phosphorylation of beta catenin. We evaluated this assumption using two cell lines. First, using temperature-sensitive v-src-transfected MDCK cells, we analyzed the modulation of cadherin-based cell adhesion by tyrosine phosphorylation. Cell aggregation and dissociation assays at nonpermissive and permissive temperatures indicated that elevation of the tyrosine phosphorylation does not totally affect the cell adhesion ability of cadherin but shifts it from a strong to a weak state. The tyrosine phosphorylation levels of beta catenin, ZO-1, ERM (ezrin/radixin/moesin), but not alpha catenin, vinculin, and alpha-actinin, were elevated in the weak state. To evaluate the involvement of the tyrosine phosphorylation of beta catenin in this shift of cadherin-based cell adhesion, we introduced v-src kinase into L fibroblasts expressing the cadherin-alpha catenin fusion protein, in which beta catenin is not involved in cell adhesion. The introduction of v-src kinase in these cells shifted their adhesion from a strong to a weak state. These findings indicated that the tyrosine phosphorylation of beta catenin is not required for the strong-to-weak state shift of cadherin-based cell adhesion, but that the tyrosine phosphorylation of other junctional proteins, ERM, ZO-1 or unidentified proteins is involved.
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PMID:V-src kinase shifts the cadherin-based cell adhesion from the strong to the weak state and beta catenin is not required for the shift. 855 50

The integrity of the vascular endothelium is mainly dependent upon the organization of interendothelial adherens junctions (AJ). These junctions are formed by the homotypic interaction of a transmembrane protein, vascular endothelial cadherin (VE-cadherin), which is complexed to an intracellular protein network including alpha-, beta-, and gamma-catenin. Additional proteins such as vinculin and alpha-actinin have been suggested to link the VE-cadherin/catenin complex to the actin-based cytoskeleton. During the process of hematogenous metastasis, circulating tumor cells must disrupt these intercellular junctions in order to extravasate. In the present study, we have investigated the influence of tumor cell-endothelial cell interaction upon interendothelial AJ. We show that human breast adenocarcinoma cells (MCF-7), but not normal human mammary epithelial cells, induce a rapid endothelial cell (EC) dissociation which correlates with the loss of VE-cadherin expression at the site of tumor cell-EC contact and with profound changes in vinculin distribution and organization. This process could not be inhibited by metalloproteinase nor serine protease inhibitors. Immunoprecipitations and Western blot analysis demonstrate that the overall expression of VE-cadherin and vinculin as well as the composition of the VE-cadherin/catenins complex are not affected by tumor cells while the tyrosine phosphorylation status of proteins within the complex is significantly altered. Our data suggest that tumor cells modulate AJ protein distribution and phosphorylation in EC and may, thereby, facilitate EC dissociation.
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PMID:Alteration of interendothelial adherens junctions following tumor cell-endothelial cell interaction in vitro. 943 30

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


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