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)

p120cas (CAS) is a protein tyrosine kinase substrate that associates directly with the cytoplasmic tail of the cell-cell adhesion molecule E-cadherin. CAS is thus part of a multimolecular complex that, along with other cadherin-binding proteins (catenins), mediates interactions between E-cadherin and the actin cytoskeleton. Down-regulation of E-cadherin expression and defects in catenin function have been implicated in tumor metastasis, but the role of CAS in these processes has not been addressed. Recently, the study of CAS was complicated when new anti-CAS antibodies revealed the presence of at least four putative CAS isoforms that appeared to vary in abundance between cell types. Here, we identify the four major isoforms expressed in murine fibroblasts, and we show that they are products of alternative splicing. Analysis of CAS isoforms in a variety of murine cell lines indicates that motile cells like fibroblasts and macrophages preferentially express CAS1 (i.e., CAS1A and CAS1B isoforms), and epithelial cells preferentially express CAS2 (i.e., CAS2A and CAS2B isoforms), whereas nonadherent cells (e.g., B cells, T cells, and myeloid cells) do not express detectable levels of CAS. Interestingly, CAS1 expression is dramatically up-regulated in a Src-transformed Madin-Darby canine kidney cell line, indicating that the pattern of isoform expression can be altered by cell transformation. Analysis of a variety of differentiated and metastatic human tumor cell lines reveals that CAS isoform expression in these cells is quite heterogeneous. Furthermore, several poorly differentiated cell lines fail to express particular isoforms that are typically observed in well-differentiated cell lines. These data raise the possibility that unbalanced expression of CAS isoforms in human carcinomas may influence cadherin function and contribute to malignant or metastatic cell phenotypes.
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PMID:Identification of murine p120 isoforms and heterogeneous expression of p120cas isoforms in human tumor cell lines. 865 9

The zonula adherens (ZA) is a cell-cell adherens junction that forms a belt in the apical most region of the lateral cell surface of many epithelia. It is composed of the cadherin-catenin complex and many associated proteins and is connected to a prominent belt of microfilaments. The ZA is believed to play an important role in the differentiation and behavior of epithelial tissues and thus contributes substantially to embryonic morphogenesis. In Drosophila embryos the ZA is formed during and shortly after gastrulation from adherens junction material that appears on the cell surface during cellularization. A ZA is present in a subset of epithelia in the Drosophila embryo called primary epithelia. A second specific marker for primary epithelia is the Crumbs protein, which in concert with the gene product of stardust is required to maintain epithelial polarity. This report shows that both genes are required for the reorganization of adherens junction material into the ZA. Using immunoelectron microscopy it is shown that Crumbs is not a component of the ZA but is distributed over the entire apical cell surface and concentrated in the immediate vicinity of the ZA. These results indicate a rather direct requirement of an apical activity for the organization of the lateral membrane domain in Drosophila primary epithelia. It is proposed that the marginal zone of the apical cell surface contains a crumbs- and stardust-dependent retention mechanism for adherens junction material that aids in the formation of the ZA.
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PMID:Crumbs, a component of the apical membrane, is required for zonula adherens formation in primary epithelia of Drosophila. 866 Aug 89

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

The APC gene is mutated in familial adenomatous polyposis and sporadic colorectal tumors. The product of this gene is a 300 kDa cytoplasmic protein associated with catenin. In the present study, we examined the subcellular localization of the APC protein and beta-catenin in the mouse colon by double-labeling immunocytochemistry. While the APC protein was localized in the lateral and apical cytoplasm and in microvilli of the epithelial cells, beta-catenin was present exclusively in the lateral cytoplasm. Double-labeling-immunoelectron microscopy demonstrated precise colocalization of the APC protein and beta-catenin along the lateral plasma membrane. These results suggest that the APC protein functions in cooperation with beta-catenin in the lateral cytoplasm but has other functions independent of beta-catenin in the apical cytoplasm and in microvilli.
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PMID:The tumor suppressor protein APC colocalizes with beta-catenin in the colon epithelial cells. 867 Feb 82

Expression of the cell adhesion molecule, epithelial cadherin (E-CD) and its binding proteins, alpha- and beta-catenins, in normal liver, chronic liver diseases, and hepatocellular carcinomas (HCCs) was investigated immunohistologically. In normal liver, weak immunostaining of E-CD and catenins was observed at the lateral membranes of the hepatocytes, whereas at the interlobular bile duct epithelia, they stained strongly. No immunoreactions were seen in sinusoidal Kupffer cells. Similar results were observed in the majority of livers from chronic hepatitis and cirrhosis sufferers; however, hepatocytes undergoing regeneration and rosette formation, as well as Hering canals and proliferating ductules, showed markedly increased molecular expression. Analysis of 66 HCC lesions revealed that the majority (64.3-96.6%) of thin trabecular- and pseudoglandular-type tumors preserved or overexpressed E-CD and catenins, whereas thick trabecular-type HCCs frequently showed low E-CD and alpha-catenin expression (56.5-65.2% reduction), suggesting that the thick trabecular histology represented diffuse tumor cell growth. Likewise, the E-CD and catenin expression levels correlated with the HCC cell differentiation grades. These collective results indicate that intercellular adhesion mediated by the E-CD-catenin system plays a role in morphological changes in nonmalignant and malignant hepatic diseases.
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PMID:Expression of epithelial cadherin and alpha- and beta-catenins in nontumoral livers and hepatocellular carcinomas. 867 62

The scenario of multistep of stomach carcinogenesis differs depending on the two histological types, well differentiated adenocarcinoma and poorly differentiated adenocarcinoma, because the two types may have different genetic pathways. Genetic instability, reactivation of telomerase and abnormal transcript of CD44 including intron 9 are common events of both well and poorly differentiated type carcinomas. These occur at early stage of carcinogenesis, even in precancerous lesions such as intestinal metaplasia and adenoma. Inactivation of APC, activation of K-ras, amplification of c-erbB2, and allelic loss of DCC locus are associated with well differentiated type, while amplification of K-sam and functional loss of cadherin/catenin are characteristics of poorly differentiated type. HGF/c-met system plays a pivotal role in morphogenesis of both histological types through interaction with cell-cell adhesion molecules. Reactivation of telomerase or genetic instability may be an initial event for accumulation of multiple genetic alterations during the progression of stomach carcinogenesis.
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PMID:[Genetic alterations in stomach cancer]. 869 39

Cadherins are homotypic adhesion molecules that classically mediate interactions between cells of the same type in solid tissues. In addition, E-cadherin is able to support homotypic adhesion of epidermal Langerhans cells to keratinocytes (Tang, A., Amagai, M., Granger, L. G., Stanley, J. R. & Udey, M. C. (1993) Nature (London) 361, 82-85) and heterotypic adhesion of mucosal epithelial cells to E-cadherin-negative intestinal intraepithelial T lymphocytes. Thus, we hypothesized that cadherins may play a wider role in cell-to-cell adhesion events involving T lymphocytes. We searched for a cadherin or cadherins in T lymphocytes with a pan-cadherin antiserum and antisera against alpha- or beta-catenin, molecules known to associate with the cytoplasmic domain of cadherins. The anti-beta-catenin antisera coimmunoprecipitated a radiolabeled species in T-lymphocyte lines that had a molecular mass of 129 kDa and was specifically immunoblotted with the pan-cadherin antiserum. Also, the pan-cadherin antiserum directly immunoprecipitated a 129-kDa radiolabeled species from an 125I surface-labeled Jurkat human T-cell leukemic cell line. After V8 protease digestion, the peptide map of this pan-cadherin-immunoprecipitated, 129-kDa species exactly matched that of the 129-kDa species coimmunoprecipitated with the beta-catenin antiserum. These results demonstrate that T lymphocytes express a catenin-associated protein that appears to be a member of the cadherin superfamily and may contribute to T cell-mediated immune surveillance.
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PMID:Expression of a candidate cadherin in T lymphocytes. 869 57

1. HT-29 M6 cells are a subpopulation of HT-29 cells that, contrarily to the parental cells, establish tight cell contacts and differentiate. Cell-to-cell contacts in HT-29 M6 cells are also regulated by protein kinase C; addition of the phorbol ester phorbol 12-myristate 13-acetate (PMA) decreases the homotypic contacts of these cells. We show here that HT-29 cells or HT-29 M6 cells treated with PMA contain lower levels of functional E-cadherin, determined by analysing the association of this protein with the cytoskeleton. No significant differences in the localization of alpha-, beta-, or p120-catenins were detected under the three different conditions. 2. Dysfunction of E-cadherin can be reversed by incubation of HT-29 cells with the tyrosine kinase inhibitor herbimycin A. On the other hand an augmentation of c-src activity in HT-29 cells or HT-29 M6 cells treated with PMA was observed with respect to control HT-29 M6 cells. The phosphorylation status of catenins was also investigated; in HT-29 or in HT-29 M6 cells treated with PMA, dysfunction of E-cadherin was accompanied by an increased phosphorylation of p120-catenin and by an elevated association of this protein to E-cadherin. These results suggest a role for pp60src and the pp60src substrate p120-catenin in the control of E-cadherin function in HT-29 cells.
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PMID:Intestinal HT-29 cells with dysfunction of E-cadherin show increased pp60src activity and tyrosine phosphorylation of p120-catenin. 869 75

DNA sequences encoding a novel member of the receptor protein tyrosine phosphatase (R-PTP) family, termed PCP-2, were identified in a human pancreatic adenocarcinoma cDNA library. Human PCP-2 cDNA predicts a protein of 1430 amino acids with a calculated Mr of 160 kDa. The predicted PCP-2 enzyme consists of a 740 amino acid extracellular region, a single transmembrane domain, and a 666 amino acid intracellular portion. The extracellular sequence contains a MAM (meprin/A5/PTPmu) domain, an immunoglobulin-like domain and four fibronectin type III-like repeats, suggesting that it is a member of the PTPkappa and PTPmu subfamily. The intracellular region contains two tandemly-repeated protein tyrosine phosphatase domains. Northern blot analyses revealed a single transcript of 5.5 kilobases, which is expressed at different levels in many human tissues except spleen and placenta. Upon transfection of PCP-2 cDNA into human embryonic kidney fibroblast 293 cells, a protein with an apparent Mr of 180 000 was detected by immunoblot analysis. This size was reduced to the predicted Mr upon treatment with endoglycosidase F, indicating that PCP-2 is glycosylated and, hence, expressed at the cell surface. A potential role of PCP-2 in cell-cell recognition and adhesion is supported by its co-localization with cell adhesion molecules, such as catenin and E-cadherin, at sites of cell-cell contact.
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PMID:Characterization of PCP-2, a novel receptor protein tyrosine phosphatase of the MAM domain family. 870 May 14

A number of genetic changes have been documented in prostate cancer, ranging from allelic loss to point mutations and changes in DNA methylation patterns. Up to now among the most consistent changes are those of allelic loss events, with the majority of tumours examined showing loss of alleles from at least one chromosomal arm. Chromosomes 8 and 13 appear to be the most frequently affected, with the former showing both loss of alleles from the short arm and gain of sequences on the long arm. Deletions of one copy of the RB gene are common, whereas deletion and/or point mutation of the TP53 gene is a less frequent event, at least in clinically localized tumours. Alterations in the E-cadherin/alpha catenin mediated cell-cell adhesion mechanism appear to be present in over one third of all prostate cancers and may be critical to the acquisition of metastatic potential of aggressive prostate cancers. In addition, altered DNA methylation patterns have been found in the majority of prostate cancers examined, suggesting an important role for methylation modulated gene expression in prostate carcinogenesis. Finally, the existence of prostate cancer susceptibility genes is suggested by study of familial clustering of prostate cancer, and it is expected that the identification of these genes will provide insight into critical rate limiting steps in the carcinogenic pathway of both inherited and sporadic disease.
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PMID:Molecular genetics of prostate cancer. 871 27


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