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 calcium-dependent class of cell adhesion molecules known as cadherins mediate homotypic cell interactions in most epithelia. We have now investigated the expression and distribution of cadherins and cadherin-associated molecules in the developing and maturing rat testis. E-Cadherin was not detected in the seminiferous tubule at any time in development or in the adult. In contrast, Leydig cells expressed E-cadherin between day 15 of gestation and postnatal day 3. alpha- and beta-catenins were expressed throughout the developing testis, but were particularly prominent in Leydig cells. In the maturing testis, alpha-catenin and plakoglobin became progressively more restricted to the basal part of the seminiferous epithelium and by 23 days exhibited a pattern characteristic of the Sertoli cell junctional complex. beta-Catenin recruitment to the Sertoli cell junctional complex was not complete until 60 days. alpha-Catenin and plakoglobin were not present at sites of Sertoli cell-germ cell contacts. Northern blot analysis of testicular RNA showed three mRNA species hybridizing with N-cadherin cDNA. A pan-cadherin antibody specific for a region of the highly conserved C-terminal of all cadherins stained sites of Sertoli-spermatocyte and Sertoli-round spermatid contact in the adult rat seminiferous epithelium, but did not stain the Sertoli cell tight junctional complex. Western blots of testicular extracts indicated that the molecule(s) recognized by these antibodies had an approximate molecular mass of 120 kilodalton, typical of members of the cadherin family. Therefore, although Sertoli cells do not express E-cadherin, another member(s) of the cadherin family is present in the testis, but may not be directly involved in tight junction dynamics as in other cells. Instead, cadherin-mediated adhesion is likely to be involved in Sertoli cell-germ cell interactions. As catenins are not present at these sites, our results suggest a catenin-independent role of cadherins in germ cell adhesion to Sertoli cells.
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PMID:Cadherins and cadherin-associated molecules in the developing and maturing rat testis. 750 30

Cadherin cell adhesion molecules play an essential role in creating tight intercellular association and are considered to work as an invasion suppressor system of cancer cells. They form a molecular complex with catenins, a group of cytoplasmic proteins including alpha- and beta-catenins. While alpha-catenin has been demonstrated to be crucial for cadherin function, the role of beta-catenin is not yet fully understood. In this study, we analyzed the cadherin-catenin system in two human cell lines, HSC-39 and its putative subline HSC-40A, derived from a signet ring cell carcinoma of stomach. These cells grow as loose aggregates or single cells, suggesting that their cadherin system is not functional. In these cell lines, an identical 321-base pair in-frame mRNA deletion of beta-catenin was identified; this led to a 107-amino-acid deletion in the NH2-terminal region of the protein. Southern blot analysis disclosed a homozygous deletion in part of the beta-catenin gene. On the other hand, these cells expressed E-cadherin, alpha-catenin, and plakoglobin of normal size. Immunoprecipitation analyses showed that E-cadherin was coprecipitated with the mutated beta-catenin but not with alpha-catenin, and antibodies against beta-catenin did not copurify alpha-catenin. However, the recombinant fusion protein containing wild-type beta-catenin precipitated alpha-catenin from these cells. These results suggest that the dysfunction of E-cadherin in these cell lines is due primarily to its failure to interact with alpha-catenin, and that this defect results from the mutation in beta-catenin. Thus, it is most likely that the association between E-cadherin and alpha-catenin is mediated by beta-catenin, and that this process is blocked by NH2-terminal deletion in beta-catenin. These findings indicate that genetic abnormality of beta-catenin is one of the mechanisms responsible for loosening of cell-cell contact, and may be involved in enhancement of tumor invasion in human cancers.
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PMID:A truncated beta-catenin disrupts the interaction between E-cadherin and alpha-catenin: a cause of loss of intercellular adhesiveness in human cancer cell lines. 795 78

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

Cadherin and catenin compose cell adhesion complex and are indispensable for tight cell-cell adhesion. Dysfunction of this adhesion complex causes dissociation of cancer cells from primary tumor nodules, thus possibly contributing to cancer invasion and metastasis. In this report, we present the human alpha-catenin sequence. Human alpha-catenin showed extensive homology with that of mouse, i.e., 91.8% and 99.3% at the nucleic acid and amino acid levels, respectively, indicating that this molecule has been evolutionarily conserved in mammals. Characterization of the mRNA sequence of alpha-catenin in PC9 was also carried out, and two distinct abnormal sequences, i.e., one of 957 bp deletion resulting in a 319-amino-acid deletion and another of 761 bp deletion resulting in a frameshift, were identified. These deletions were probably produced by an error of RNA splicing, presenting one possible mechanism for the loss of intact alpha-catenin expression.
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PMID:Cloning of the human alpha-catenin cDNA and its aberrant mRNA in a human cancer cell line. 832 64

Vascular endothelial cadherin (VE-cadherin, cadherin-5, or 7B4) is an endothelial specific cadherin that regulates cell to cell junction organization in this cell type. Cadherin linkage to intracellular catenins was found to be required for their adhesive properties and for localization at cell to cell junctions. We constructed a mutant form of VE-cadherin lacking the last 82 amino acids of the cytoplasmic domain. Surprisingly, despite any detectable association of this truncated VE-cadherin to catenin-cytoskeletal complex, the molecule was able to cluster at cell-cell contacts in a manner similar to wild type VE-cadherin. Truncated VE-cadherin was also able to promote calcium-dependent cell to cell aggregation and to partially inhibit cell detachment and migration from a confluent monolayer. In contrast, intercellular junction permeability to high molecular weight molecules was severely impaired by truncation of VE-cadherin cytoplasmic domain. These results suggest that the VE-cadherin extracellular domain is enough for early steps of cell adhesion and recognition. However, interaction of VE-cadherin with the cytoskeleton is necessary to provide strength and cohesion to the junction. The data also suggest that cadherin functional regulation might not be identical among the members of the family.
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PMID:Catenin-dependent and -independent functions of vascular endothelial cadherin. 853 53

Cadherins are transmembrane receptors with an extracellular domain that participates in homophilic cell to cell adhesion and a cytoplasmic domain that associates with proteins called catenins. Cadherin-mediated adhesion as well as adhesion-independent functions for catenins play important roles in differentiation, development, and malignant transformation. Mechanisms that regulate steady-state catenin levels and cadherin-catenin complex stability are poorly understood, but activities of both the Wnt-1 proto-oncogene and tyrosine kinases are implicated. Here I define, at the biochemical level, distinct mechanisms that modulate steady-state catenin levels. Increased cadherin expression, providing more catenin binding sites, leads to selective stabilization of the cadherin-associated population of alpha- and beta-catenin, but not p120(cas). In contrast, expression of Wnt-1 leads primarily to increased stability of the uncomplexed pool of beta-catenin without effect on p120(cas). Significantly, the Wnt-1-induced stabilization of uncomplexed beta-catenin is independent of cadherin expression. Transformation by v-Src does not disrupt the catenin-cadherin complex despite the phosphorylation of E-cadherin and beta-catenin on tyrosine. In contrast to the effects of Wnt-1, v-Src does not modulate the uncomplexed population of beta-catenin. p120(cas) is phosphorylated on tyrosine by v-Src, and this is accompanied by a significant decrease in the level of uncomplexed p120(cas) as well as a change in behavior of p120(cas) upon biochemical fractionation. Taken together these data suggest that p120(cas) and beta-catenin are regulated independently.
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PMID:Regulation of complexed and free catenin pools by distinct mechanisms. Differential effects of Wnt-1 and v-Src. 902 Jan 80

E-Cadherin has been shown to be an invasion tumor suppressor gene, but few epidemiological studies have revealed relationships between loss of E-cadherin expression and invasive tumor growth and/or metastasis. The adhesive function of E-cadherin is dependent on the integrity of the catenin components which link E-cadherin to the actin filaments. In order to achieve a better correlation between the loss of cell adhesion and metastasis in cancer, we decided to investigate both E-cadherin and the catenins. 157 archival primary mammary carcinomas were immunohistochemically studied using antibodies against E-cadherin, alpha-, beta- and gamma-catenin. The following results were obtained: (a) Independent of the presence of E-cadherin, loss of expression of one or multiple catenins was noted; (b) loss of E-cadherin and alpha-catenin expression was more pronounced in lobular-type than ductal-type carcinomas; c) axillary lymph node metastases were completely lacking only in the group where expression of E-cadherin, alpha- and beta- catenin was preserved: d) no correlation between expression of c-erbB-2 and E-cadherin or one of the catenins was found. The results demonstrate for the first time that consideration of both the expression of E-cadherin and of the three catenins is useful in evaluation of the metastatic potential of mammary carcinomas.
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PMID:Expression of E-cadherin and catenins in invasive mammary carcinomas. 906 80

Rat 235-1 pituitary tumor cells are lactotrophs producing high levels of prolactin (PRL). Dexamethasone (Dex, 100 nM) inhibits PRL gene expression in 235-1 cells by 50%, while simultaneously decreasing cell replication and cell-cell aggregation. To determine the time course of Dex action, we used a quantitative assay for cell-cell interaction, based on the number of single cells present before and after re-aggregation of dispersed cells. 235-1 cells were cultured in growth medium or medium plus 100 nM Dex for 1-4 days before assay. Control cells had 90% re-aggregation on all days of assay. Aggregation of Dex-treated cells decreased to 55% by day 4. Dex treatment also reduced cell numbers by 40%, but this decrease did not contribute to reduced aggregation. To determine the mechanism of Dex-inhibited cell-cell adhesion, we examined the expression of cadherins and catenins. Cadherin-related mRNAs (P- and N-cadherin probes) were detectable in 235-1 cells, but their levels were unchanged by Dex. A pancadherin antibody was unable to detect classical cadherins in these cells. Both alpha- and beta-catenins were detected by Western blotting and their levels were decreased by Dex. Unlike control aggregates, aggregates of Dex-treated cells were able to inhibit expression of PRL mRNA when added to monolayers of 235-1 cells. These data suggest that Dex influences cadherin function by inhibiting catenin expression and that this has the functional consequence of altering 235-1 cell-cell interactions. Overall the data show that Dex affects important aspects of lactotroph function other than PRL gene expression. These changes may include physical alterations in pituitary cell contacts that further support a change in functional state.
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PMID:Co-regulation of pituitary tumor cell adhesion and prolactin gene expression by glucocorticoid. 939 62

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

Cadherin-mediated adhesion depends on the association of its cytoplasmic domain with the actin-containing cytoskeleton. This interaction is mediated by a group of cytoplasmic proteins: alpha-and beta- or gamma- catenin. Phosphorylation of beta-catenin on tyrosine residues plays a role in controlling this association and, therefore, cadherin function. Previous work from our laboratory suggested that a nonreceptor protein tyrosine phosphatase, bound to the cytoplasmic domain of N-cadherin, is responsible for removing tyrosine-bound phosphate residues from beta-catenin, thus maintaining the cadherin-actin connection (). Here we report the molecular cloning of the cadherin-associated tyrosine phosphatase and identify it as PTP1B. To definitively establish a causal relationship between the function of cadherin-bound PTP1B and cadherin-mediated adhesion, we tested the effect of expressing a catalytically inactive form of PTP1B in L cells constitutively expressing N-cadherin. We find that expression of the catalytically inactive PTP1B results in reduced cadherin-mediated adhesion. Furthermore, cadherin is uncoupled from its association with actin, and beta-catenin shows increased phosphorylation on tyrosine residues when compared with parental cells or cells transfected with the wild-type PTP1B. Both the transfected wild-type and the mutant PTP1B are found associated with N-cadherin, and recombinant mutant PTP1B binds to N-cadherin in vitro, indicating that the catalytically inactive form acts as a dominant negative, displacing endogenous PTP1B, and rendering cadherin nonfunctional. Our results demonstrate a role for PTP1B in regulating cadherin-mediated cell adhesion.
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PMID:The nonreceptor protein tyrosine phosphatase PTP1B binds to the cytoplasmic domain of N-cadherin and regulates the cadherin-actin linkage. 978 60


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