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Query: UNIPROT:B0FTZ7 (catenin)
 18,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The function of cadherin cell adhesion molecules is thought to be regulated by a group of cytoplasmic proteins, including alpha-catenin. We identified a subtype of alpha-catenin, termed alpha N-catenin, which is associated with N-cadherin and expressed mainly in the nervous system. cDNA transfection experiments showed that alpha N-catenin can also bind with E-cadherin. To investigate the role of alpha N-catenin, we transfected lung carcinoma PC9 cells, which express E-cadherin and beta-catenin but neither alpha- nor alpha N-catenin, with alpha N-catenin cDNA. While parental PC9 grew as isolated cells, the transfectant lines formed aggregates in which cells were tightly adhered to each other, showing epithelial arrangements, and they occasionally gave rise to cystic spheres. These results suggest that alpha N-catenin is crucial not only for cadherin function but also for organization of multicellular structures.
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PMID:Identification of a neural alpha-catenin as a key regulator of cadherin function and multicellular organization. 163 32

The Ca(2+)-dependent cell adhesion molecule uvomorulin is a member of the cadherin gene family. Its cytoplasmic region complexes with structurally defined proteins termed alpha-, beta-, and gamma-catenins. Here we show that A-CAM (N-cadherin), another member of this gene family, also associates with catenins suggesting that this complex formation may be a general property of the cadherins. For uvomorulin it has been found that this association with catenins is of crucial importance for the adhesive function, but little is known about the molecular organization of the uvomorulin-catenin complex. Using a combination of biochemical analyses we show that a single complex is composed of one molecule of uvomorulin, one or two molecules of beta-catenin, and one molecule of alpha-catenin. Furthermore, beta-catenin seems to interact more directly with uvomorulin. In pulse-chase experiments beta-catenin is already associated with the 135-kD uvomorulin precursor molecule but the assembly of the newly synthesized alpha-catenin into the complex is only detected around the time of endoproteolytic processing.
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PMID:Molecular organization of the uvomorulin-catenin complex. 173 27

Alterations in intercellular junction and membrane cytoskeletal proteins may underlie some of the morphological, invasive and metastatic properties of cancer. E-cadherin, a transmembrane protein that functions in epithelial cell-cell interactions at adherens junctions, is linked to the membrane cytoskeletal matrix through interactions with alpha- and beta-catenin. We have carried out studies of E-cadherin and alpha- and beta-catenin in 18 breast cancer cell lines to determine the prevalence and nature of alterations in these genes in breast cancer. Ten lines failed to express E-cadherin protein at detectable levels and seven failed to produce detectable levels of E-cadherin transcripts. In a line lacking E-cadherin expression (SK-BR-3) a homozygous deletion of a large portion of the E-cadherin gene was noted. Localized sequence alterations in E-cadherin transcripts were not identified in any lines. In contrast to the results of a previous study, no relationship was identified between E-cadherin expression and HER-2/NEU expression. Two of the 18 lines had no detectable alpha-catenin protein and six others had reduced levels. The two lines lacking alpha-catenin protein had reduced or undetectable levels of alpha-catenin transcripts, while no consistent changes in alpha-catenin transcript levels were seen in the lines with reduced, but detectable, levels of alpha-catenin protein. Similarly, although two lines lacked beta-catenin protein, in most lines the levels of beta-catenin transcripts and protein were not well correlated with one another. Our findings suggest that alterations in E-cadherin and alpha- and beta-catenin expression are frequent in human breast cancer-derived cell lines, and that in some cases the decreased expression may result from mutations in the genes. Furthermore, the frequent alterations in the expression of these proteins argue that loss of function in the E-cadherin-catenin pathway may be critical in the development of many breast cancers.
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PMID:Frequent alterations in E-cadherin and alpha- and beta-catenin expression in human breast cancer cell lines. 747 52

The cadherin-catenin complex has an important role in cell-cell adhesion and may also function in signaling pathways. We report that overexpression of three cadherin types in Xenopus embryos causes them to develop with reduced dorsal axial structures. The same phenotype is produced in embryos that have been depleted of maternal beta-catenin protein by an antisense oligodeoxynucleotide complementary to beta-catenin mRNA. They show an inhibition in the expression of dorsal mesodermal markers MyoD and goosecoid, but not of ventral and general mesodermal markers. They lack notochords, somites, and neural tubes and are defective in dorsal mesodermal signaling in Nieuwkoop assays. The phenotype can be rescued by the injection of beta-catenin mRNA and not by the injection of Xwnt-8 mRNA. These results show that beta-catenin has an important role in dorsal mesoderm induction. They directly demonstrate the activity of a maternal mRNA in axis specification.
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PMID:Overexpression of cadherins and underexpression of beta-catenin inhibit dorsal mesoderm induction in early Xenopus embryos. 752 1

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

Cadherins and catenins play an important role in cell-cell adhesion. Two of the catenins, beta and gamma, are members of a group of proteins that contains a repeating amino acid motif originally described for the Drosophila segment polarity gene armadillo. Another member of this group is a 120-kD protein termed p120, originally identified as a substrate of the tyrosine kinase pp60src. In this paper, we show that endothelial and epithelial cells express p120 and p100, a 100-kD, p120-related protein. Peptide sequencing of p100 establishes it as highly related to p120. p120 and p100 both appear associated with the cadherin/catenin complex, but independent p120/catenin and p100/catenin complexes can be isolated. This association is shown by coimmunoprecipitation of cadherins and catenins with an anti-p120/p100 antibody, and of p120/p100 with cadherin or catenin antibodies. Immunocytochemical analysis with a p120-specific antibody reveals junctional colocalization of p120 and beta-catenin in epithelial cells. Catenins and p120/p100 also colocalize in endothelial and epithelial cells in culture and in tissue sections. The cellular content of p120/p100 and beta-catenin is similar in MDCK cells, but only approximately 20% of the p120/p100 pool associates with the cadherin/catenin complex. Our data provide further evidence for interactions among the different arm proteins and suggest that p120/p100 may participate in regulating the function of cadherins and, thereby, other processes influenced by cell-cell adhesion.
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PMID:p120, a p120-related protein (p100), and the cadherin/catenin complex. 761 37

The extracellular segment of the receptor-type type protein tyrosine phosphatase PTPmu, possesses an MAM domain, an immunoglobulin domain, and four fibronectin type-III repeats. It binds homophilically, i.e., PTPmu on the surface of one cell binds to PTPmu on an apposing cell, and the binding site lies within the immunoglobulin domain. The intracellular segment of PTPmu has two PTP domains and a juxtamembrane segment that is homologous to the conserved intracellular domain of the cadherins. In cadherins, this segment interacts with proteins termed catenins to mediate association with the actin cytoskeleton. In this article, we demonstrate that PTPmu associates with a complex containing cadherins, alpha- and beta-catenin in mink lung (MvLu) cells, and in rat heart, lung, and brain tissues. Greater than 80% of the cadherin in the cell is cleared from Triton X-100 lysates of MvLu cells after immunoprecipitation with antibodies to PTPmu; however, the complex is dissociated when lysates are prepared in more stringent, SDS-containing RIPA buffer. In vitro binding studies demonstrated that the intracellular segment of PTPmu binds directly to the intracellular domain of E-cadherin, but not to alpha- or beta-catenin. Consistent with their ability to interact in vivo, PTPmu, cadherins, and catenins all localized to points of cell-cell contact in MvLu cells, as assessed by immunocytochemical staining. After pervanadate treatment of MvLu cells, which inhibits cellular tyrosine phosphatase activity including PTPmu, the cadherins associated with PTPmu are now found in a tyrosine-phosphorylated form, indicating that the cadherins may be an endogenous substrate for PTPmu. These data suggest that PTPmu may be one of the enzymes that regulates the dynamic tyrosine phosphorylation, and thus function, of the cadherin/catenin complex in vivo.
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PMID:Receptor protein tyrosine phosphatase PTPmu associates with cadherins and catenins in vivo. 764 13

The tyrosine kinase substrate p120cas (CAS), which is structurally similar to the cell adhesion proteins beta-catenin and plakoglobin, was recently shown to associate with the E-cadherin-catenin cell adhesion complex. beta-catenin, plakoglobin, and CAS all have an Arm domain that consists of 10 to 13 repeats of a 42-amino-acid motif originally described in the Drosophila Armadillo protein. To determine if the association of CAS with the cadherin cell adhesion machinery is similar to that of beta-catenin and plakoglobin, we examined the CAS-cadherin-catenin interactions in a number of cell lines and in the yeast two-hybrid system. In the prostate carcinoma cell line PC3, CAS associated normally with cadherin complexes despite the specific absence of alpha-catenin in these cells. However, in the colon carcinoma cell line SW480, which has negligible E-cadherin expression, CAS did not associate with beta-catenin, plakoglobin, or alpha-catenin, suggesting that E-cadherin is the protein which bridges CAS to the rest of the complex. In addition, CAS did not associate with the adenomatous polyposis coli (APC) tumor suppressor protein in any of the cell lines analyzed. Interestingly, expression of the various CAS isoforms was quite heterogeneous in these tumor cell lines, and in the colon carcinoma cell line HCT116, which expresses normal levels of E-cadherin and the catenins, the CAS1 isoforms were completely absent. By using the yeast two-hybrid system, we confirmed the direct interaction between CAS and E-cadherin and determined that CAS Arm repeats 1 to 10 are necessary and sufficient for this interaction. Hence, like beta-catenin and plakoglobin, CAS interacts directly with E-cadherin in vivo; however, unlike beta-catenin and plakoglobin, CAS does not interact with APC or alpha-catenin.
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PMID:The tyrosine kinase substrate p120cas binds directly to E-cadherin but not to the adenomatous polyposis coli protein or alpha-catenin. 765 99

Association of the c-erbB-2 oncogene product with the cadherin-catenin complex has been demonstrated in human cancer cell lines. Although beta-catenin and plakoglobin have been proven to be crucial for the association, no previous study has shown whether the interactions are direct or indirect. In the present study, the c-erbB-2 gene product was shown by far-Western blotting analysis to associate directly with both beta-catenin and plakoglobin through its cytoplasmic domain core region, which showed extensive homology with epidermal growth factor receptor. These data suggest that c-erbB-2-induced signaling is also directly liked to the cadherin-mediated cell adhesion and "invasion-suppressor" system through beta-catenin and plakoglobin in cancers.
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PMID:c-erbB-2 gene product directly associates with beta-catenin and plakoglobin. 770 5

The cytoplasmic domain of classical cadherins is tightly associated with three proteins termed alpha-, beta- and gamma-catenin. These accessory proteins are of central importance for the adhesive properties of this class of cell adhesion molecules. In order to examine the molecular architecture of the cadherin-catenin complex in more detail we have expressed the catenins and the cytoplasmic domain of E-cadherin as fusion proteins in Escherichia coli, and analyzed the interaction of purified recombinant cadherin and catenins in combinatorial protein-protein interaction experiments. The cytoplasmic domain of E-cadherin cannot directly associate with alpha-catenin but interacts with high affinity with beta-catenin, whereas the binding of gamma-catenin (plakoglobin) to E-cadherin is less efficient. alpha- and beta-catenin assemble into a 1:1 heterodimeric complex. The analysis of various truncated beta-catenins revealed that an alpha-catenin binding site in beta-catenin is localized between amino acid positions 120 and 151. The central role of beta-catenin for the assembly of the heterotrimeric E-cadherin/alpha-catenin/beta-catenin complex in mixing experiments with all components was demonstrated. The reconstitution in vitro of the cadherin-catenin complex should allow the study of the interaction with signalling molecules and with the actin-based cytoskeleton.
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PMID:Assembly of the cadherin-catenin complex in vitro with recombinant proteins. 770 14


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