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

Three cytoplasmic proteins, called catenins, bind to the cytoplasmic tail of the epithelial cell-cell adhesion molecule E-cadherin. The complementary DNA sequence was determined for the 92-kilodalton beta catenin of Xenopus laevis. The sequence is homologous to mammalian plakoglobin, a protein of desmosomal and zonula adherens cell junctions, and to the plakoglobin homolog in Drosophila melanogaster, the product of the segment polarity gene armadillo. A monoclonal antibody to bovine plakoglobin recognizes the analogous beta catenin in the Madin-Darby canine kidney (MDCK) cell line. Armadillo plakoglobin may link E-cadherin to the underlying actin cytoskeleton at cell-cell junctions; the E-cadherin-catenin protein complex may also participate in the transmission of developmental information.
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PMID:A homolog of the armadillo protein in Drosophila (plakoglobin) associated with E-cadherin. 196 94

The carboxyl terminus-truncated cadherin (nonfunctional cadherin) has no cell adhesion activity probably because of its failure to associate with cytoplasmic proteins called alpha and beta catenin. To rescue this nonfunctional cadherin as adhesion molecules, we constructed three cDNAs for fusion proteins between nonfunctional E-cadherin and alpha catenin, nE alpha, nE alpha N, and nE alpha C, where the intact, amino-terminal and carboxy-terminal half of alpha catenin, respectively, were directly linked to the nonfunctional E-cadherin, and introduced them into mouse L cells. The subcellular distribution and cell adhesion activity of nE alpha and nE alpha C molecules was similar to those of intact E-cadherin transfectants: they bound to cytoskeletons, were concentrated at cell-cell adhesion sites and showed strong cell adhesion activity. nE alpha N molecules, which also bound to cytoskeletons, showed very poor cell adhesion activity. Taken together, we conclude that in the formation of the cadherin-catenin complex, the mechanical association of alpha catenin, especially its carboxy-terminal half, with E-cadherin is a key step for the cadherin-mediated cell adhesion. Close comparison revealed that the behavior of nE alpha molecules during cytokinesis was quite different from that of intact E-cadherin, and that the intercellular motility, i.e., the cell movement in a confluent sheet, was significantly suppressed in nE alpha transfectants although it was facilitated in E-cadherin transfectants. Considering that nE alpha was not associated with endogenous beta catenin in transfectants, the difference in the nature of cell adhesion between nE alpha and intact E-cadherin transfectants may be explained by the function of beta catenin. The possible functions of beta catenin are discussed with a special reference to its role as a negative regulator for the cadherin-mediated cell adhesion system.
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PMID:The roles of catenins in the cadherin-mediated cell adhesion: functional analysis of E-cadherin-alpha catenin fusion molecules. 792 66

Cadherin cell-cell adhesion molecules are associated with cytoskeletal proteins, including alpha and beta catenin, and plakoglobin. This cadherin-catenin complex plays an indispensable role in construction of ordered multicellular structures such as polarized epithelium. alpha-catenin is crucial for the cell binding function of cadherins; without it, cells cannot use the cadherin adhesion system for their adhesion. beta-catenin and plakoglobin possibly play more regulatory roles, as it was shown that their tyrosine phosphorylation correlated with modified cadherin activities. The expression of some cadherin-associated proteins is controlled by the wingless/Wnt-1 signal in embryos. These regulatory mechanisms of cadherin function and expression may be involved in dynamic control of cell-cell contacts during morphogenesis, and even in certain processes of cell growth and differentiation.
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PMID:Dynamic control of cell-cell adhesion for multicellular organization. 807 12

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

Catenins (alpha, beta, and gamma) are a group of proteins linking E-cadherin with the cytoskeleton. Reduced expression of alpha catenin has been shown in some cancer lines and tissues and is related to the invasive nature of tumour cells. This study examined the effects of n-6 PUFAs on the expression of catenins in a range of human cancer cells by Western blotting. Although most of the cell lines expressed similar levels of beta and gamma catenins, a number of cell lines expressed low levels of alpha catenin. Treatment of cells with gamma linolenic acid (GLA) increased alpha catenin expression in most cell lines, while beta catenin levels were reduced, and gamma catenin expression was unchanged. Linoleic acid and arachidonic acid had not significant effects. We conclude that in human cancer cell lines, the expression of alpha and beta catenins can be regulated by gamma linolenic acid.
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PMID:Expression of catenins in human cancer cells and its regulation by n-6 polyunsaturated fatty acids. 866 25

ZO-1, a 220-kD peripheral membrane protein consisting of an amino-terminal half discs large (dlg)-like domain and a carboxyl-terminal half domain, is concentrated at the cadherin-based cell adhesion sites in non-epithelial cells. We introduced cDNAs encoding the full-length ZO-1, its amino-terminal half (N-ZO-1), and carboxyl-terminal half (C-ZO-1) into mouse L fibroblasts expressing exogenous E-cadherin (EL cells). The full-length ZO-1 as well as N-ZO-1 were concentrated at cadherin-based cell-cell adhesion sites. In good agreement with these observations, N-ZO-1 was specifically coimmunoprecipitated from EL transfectants expressing N-ZO-1 (NZ-EL cells) with the E-cadherin/alpha, beta catenin complex. In contrast, C-ZO-1 was localized along actin stress fibers. To examine the molecular basis of the behavior of these truncated ZO-1 molecules, N-ZO-1 and C-ZO-1 were produced in insect Sf9 cells by recombinant baculovirus infection, and their direct binding ability to the cadherin/catenin complex and the actin-based cytoskeleton, respectively, were examined in vitro. Recombinant N-ZO-1 bound directly to the glutathione-S-transferase fusion protein with alpha catenin, but not to that with beta catenin or the cytoplasmic domain of E-cadherin. The dissociation constant between N-ZO-1 and alpha catenin was approximately 0.5 nM. On the other hand, recombinant C-ZO-1 was specifically cosedimented with actin filaments in vitro with a dissociation constant of approximately 10 nM. Finally, we compared the cadherin-based cell adhesion activity of NZ-EL cells with that of parent EL cells. Cell aggregation assay revealed no significant differences among these cells, but the cadherin-dependent intercellular motility, i.e., the cell movement in a confluent monolayer, was significantly suppressed in NZ-EL cells. We conclude that in nonepithelial cells, ZO-1 works as a cross-linker between cadherin/catenin complex and the actin-based cytoskeleton through direct interaction with alpha catenin and actin filaments at its amino- and carboxyl-terminal halves, respectively, and that ZO-1 is a functional component in the cadherin-based cell adhesion system.
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PMID:Involvement of ZO-1 in cadherin-based cell adhesion through its direct binding to alpha catenin and actin filaments. 921 91

The cell undergoes a diverse range of stimulations including growth factor activation and signal transduction from adhesion receptors, such as cadherins. In the absence of a mitogenic signal from outside the cell, beta catenin is sequestered in complexes with the product of the adenomatous polyposis coli (APC) gene and a serine threonine glycogen kinase (GSK 3 beta) enabling degradation of free beta catenin. Residual catenins hold cells together by binding to cadherins both at adherens junctions and the actin cytoskeleton. When a mitotic signal is delivered by the wnt pathway, GSK 3 beta is antagonised so that beta catenin can no longer be degraded. Cytosolic concentrations rise and binding to other newly synthesised proteins occurs, especially transcription factors that are transported to the nucleus, such as lymphocyte enhancing factor and T cell factor. This article discusses the signalling between mitogenic and adhesion pathways and suggests that it is a global mechanism for development, differentiation, and disease. These changes in catenin and APC biology may not be sufficient alone to transform cells fully but they appear to be a necessary final common pathway for several cancers of the mucous secreting crypts (including Barrett's oesophageal lesions and colorectal cancer) or stratified secreting epithelium (melanoma) before invasion.
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PMID:Cadherin and catenin biology represent a global mechanism for epithelial cancer progression. 953 77

Normal Human Keratinocytes express on their cell surface E- and P-cadherins, two Ca2+ dependent homophilic cell adhesion molecules that mediate keratinocyte-keratinocyte adherens junctions. In other cell types, adherens-type junctions are reported to be major subcellular targets for tyrosine specific protein phosphorylation (Volberg et al. (1991) Cell Regul., 2, 105-120) involving tyrosine kinases and tyrosine phosphatases. We investigated the role of tyrosine phosphatases in the regulation of cadherin mediated keratinocyte-keratinocyte adhesion. We report the results of a wide tyrosine phosphatase inhibition using pervanadate, a modified vanadate derivative known to inhibit most tyrosine phosphatases. Keratinocytes treated with pervanadate, exhibit an important change in cellular morphology and cadherins/catenins localization as shown by phase contrast microscopy and immunocytochemistry. In this conditions, cadherins and catenins no longer colocalize with the actin cytoskeleton of cells and the amount of E-cadherin bound to the cytoskeleton decreases. A more intense phosphotyrosine labelling is seen at the edges of the treated cells, suggesting that an increase in the phosphorylation rate of some cadherin-catenin complex proteins induces a diminished intercellular adhesion. Finally immunoprecipitation experiments of the E-cadherin/catenin complex from pervanadate treated keratinocytes reveal an increase in the tyrosine phosphorylation rate of E-cadherin, beta catenin and probably gamma catenin. These data suggest an essential role for the protein tyrosine phosphatases in keratinocyte intercellular junctions.
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PMID:Cadherin mediated cell-cell adhesion is regulated by tyrosine phosphatases in human keratinocytes. 963 38

Caspase-mediated proteolysis of cytoskeletal proteins during apoptosis appears to be commonplace. Enlarging on previous studies we have shown here that gamma catenin, like beta catenin, was degraded during cisplatin-induced apoptosis, initially giving a major product of 75 kDa. This truncated protein could be co-immunoprecipitated with alpha catenin. Addition of caspase inhibitors to cells in the presence of cisplatin appreciably reduced the proteolysis of gamma catenin as well as the level of apoptosis. Only limited degradation of alpha catenin was observed even at very late times when over 90% of cells in the culture were apoptotic. Immunohistochemical staining showed that during apoptosis there was a relocation of alpha, beta, and gamma catenin from the periphery of the cell to the cytoplasm, at the same time as other morphological changes commonly associated with apoptosis occurred. Interestingly, the changes in localisation of the catenins preceded proteolysis by several hours. In the presence of cisplatin and caspase inhibitor no change in distribution of catenins was observed, suggesting that re-localisation requires caspase activity but not necessarily directed against beta and gamma catenins.
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PMID:Specific cleavage of gamma catenin by caspases during apoptosis. 973 32

Maintenance of an adhesive function for cadherins requires appropriate membranous cellular expression and intact cadherin-catenin complexes. In normal squamous mucosa of the oesophagus there is membranous co-expression of E- and P-cadherin (E-cad, P-cad) in the basal compartment, whereas suprabasal stratification is associated with preservation of E-cad expression but loss of P-cad. Immunohistochemical staining of squamous dysplasia/carcinoma in situ shows a striking increase in the proportion of cells within the epithelial compartment showing co-expression of E- and P-cad with strong appropriate membranous expression of beta and gamma catenin. Strong membranous co-expression of E- and P-cad and beta catenin is seen on keratinocytes at the periphery of islands of invasive better-differentiated squamous carcinoma with keratinisation, mimicking normal mucosa. Beta catenin may be phosphorylated with implied loss of cadherin binding. Membranous cadherin and catenin expression is significantly down-regulated in poorly differentiated squamous carcinoma. No beta catenin mutations were demonstrated in squamous carcinomas following DNA extraction and sequencing, nor was any nuclear cadherin seen. Changes in cadherin-catenin complexes with cellular phenotype is well demonstrated in spindle cell carcinomas with a shift of cadherin expression from membranous to cytoplasmic between the epithelioid and spindle cell components of the tumour and with loss of expression in the sarcomatoid elements. In conclusion, we demonstrate an increased expression of P-cadherin early in tumourigenesis with loss of cadherin-catenin complexes in poorly differentiated invasive carcinomas. Cadherin/catenin expression may govern both the phenotype and biology of oesophageal squamous carcinomas.
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PMID:Sequential changes in cadherin-catenin expression associated with the progression and heterogeneity of primary oesophageal squamous carcinoma. 984 64


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