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

Cadherins comprise a family of cell surface, calcium-dependent cell-cell adhesion glycoproteins widely distributed in developing and mature multicellular organisms. Here we show that three distinct cadherins, (E-, P-, and N-cadherin) associate with a group of non-cadherin-related proteins, termed catenins, postulated to link cadherins to the actin-based cytoskeleton. We present evidence that the catenin repertoire is identical when different members of the cadherin family are isolated from the same cell and similar, but distinct, when isolated from different cell types and different organisms. The association of catenins with cadherins is not dependent upon cadherin assuming its calcium-dependent conformation and appears to occur prior to expression of mature, functional cadherin at the cell surface.
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PMID:Cadherins and associated proteins. 176 2

Uvomorulin belongs to the group of Ca2+-dependent cell adhesion molecules, which are integral membrane proteins with several structural features in common. In particular, the cytoplasmic part of these proteins is highly conserved in different species, suggesting a common biological function. To test this assumption we transfected a uvomorulin full-length cDNA into uvomorulin-negative mouse NIH 3T3 and L cells. Immunoprecipitations with anti-uvomorulin antibodies detected, in addition to uvomorulin, three independent proteins of 102, 88 and 80 kd which are of host origin and which form complexes with uvomorulin. Using cDNA constructs coding for uvomorulin with cytoplasmic or extracellular deletions it is shown that the 102, 88 and 80 kd proteins complex with the cytoplasmic domain of uvomorulin. Peptide pattern analysis revealed that these three proteins are identical in different mouse cells. When uvomorulin cDNA was introduced into cell lines from other species, such as human HeLa and avian fibroblasts, the expressed uvomorulin was also associated with endogenous 102, 88 and 80 kd proteins and, moreover, each of these proteins showed structural similarities to the respective mouse molecule. A panel of antibodies specific for known cytoplasmic proteins of mol. wts similar to those of the three proteins did not react with any of the described components. This suggests that the 102, 88 and 80 kd proteins constitute a new group of proteins for which we propose the nomenclature of catenin alpha, beta and gamma respectively. The characterization of these proteins provides a first molecular basis for a possible cytoplasmic anchorage of uvomorulin to the cytoskeleton.
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PMID:The cytoplasmic domain of the cell adhesion molecule uvomorulin associates with three independent proteins structurally related in different species. 278 74

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

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

The cadherin-catenin complex is important for mediating homotypic, calcium-dependent cell-cell interactions in diverse tissue types. Although proteins of this complex have been identified, little is known about their interactions. Using a genetic assay in yeast and an in vitro protein-binding assay, we demonstrate that beta-catenin is the linker protein between E-cadherin and alpha-catenin and that E-cadherin does not bind directly to alpha-catenin. We show that a 25-amino acid sequence in the cytoplasmic domain of E-cadherin and the amino-terminal domain of alpha-catenin are independent binding sites for beta-catenin. In addition to beta-catenin and plakoglobin, another member of the armadillo family, p120 binds to E-cadherin. However, unlike beta-catenin, p120 does not bind alpha-catenin in vitro, although a complex of p120 and endogenous alpha-catenin could be immunoprecipitated from cell extracts. In vitro protein-binding assays using recombinant E-cadherin cytoplasmic domain and alpha-catenin revealed two catenin pools in cell lysates: an approximately 1000- to approximately 2000-kDa complex bound to E-cadherin and an approximately 220-kDa pool that did not contain E-cadherin. Only beta-catenin in the approximately 220-kDa pool bound exogenous E-cadherin. Delineation of these molecular linkages and the demonstration of separate pools of catenins in different cell lines provide a foundation for examining regulatory mechanisms involved in the assembly and function of the cadherin-catenin complex.
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PMID:Genetic and biochemical dissection of protein linkages in the cadherin-catenin complex. 776 49

Because the cell adhesion molecule epithelial cadherin (E-cadherin) is absent in many invasive carcinomas, we transfected the E-cadherin gene into E-cadherin-negative, invasive breast cancer cell lines BT549 and HS578t to investigate the role of E-cadherin in invasive behavior. Although the transfected E-cadherin could mediate calcium-dependent aggregation to E-cadherin-transfected L-cells, morphology and invasiveness of the breast cancer cells were not altered. We investigated the strength of the linkage of the transfected E-cadherin to the actin cytoskeleton by examining the Triton X-100 solubility of the transfected E-cadherin. In BT549 and HS578t cells, a large proportion of the transfected E-cadherin was Triton soluble, whereas in E-cadherin-positive MCF-7 cells, Triton-insoluble E-cadherin was apparent at cell-cell borders. Interaction of E-cadherin with the actin cytoskeleton is thought to be mediated by the E-cadherin-binding proteins alpha-catenin, beta-catenin, and plakoglobin. We found normal levels of alpha-catenin and beta-catenin in BT549 and HS578t cells; however, low levels of plakoglobin were expressed in these cells compared to those found in weakly invasive MCF-7 cells. Furthermore, levels of tyrosine phosphorylation of beta-catenin were elevated in E-cadherin-transfected BT549 and HS578t cells compared to MCF-7 cells. We conclude that other factors such as the expression and appropriate posttranslational modification of cadherin-associated proteins must be in place for E-cadherin to be fully functional, i.e., to alter invasiveness. During cancer progression, loss of E-cadherin expression itself or multiple other mechanisms that lead to loss of cell-cell adhesion (mutation, loss of catenin expression, alterations in phosphorylation) may contribute to a more metastatic phenotype.
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PMID:Alterations in beta-catenin phosphorylation and plakoglobin expression in human breast cancer cells. 801 79

Invasion is the cause of cancer malignancy. Invasion leads to metastasis and metastases turn cancer into an incurable disease. The only model of "true" invasion and metastasis is the natural human or animal tumor. Nevertheless, experimental models have largely contributed to the development of new concepts such as the multistep invasion process of metastasis, the growth-separate-from-invasion concept and the transient expression of the invasive phenotype by a subpopulation of cancer cells. All these aspects of invasion are considered within micro-ecosystems that are initiated by the cancer cells but in which host cells may play an equally important role. It is our opinion that invasion is regulated by the balance between the activation and inactivation of two sets of genes, invasion-promoter and invasion-suppressor genes. These genes encode molecules that determine the expression of the invasive and the noninvasive (normal) phenotype. E-cadherin is an invasion-suppressor gene product that belongs to the calcium-dependent homophilic cell-cell adhesion molecules. This transmembrane glycoprotein is involved not only in the mechanics of adhesion but also serves as a signal-transducer via its linkage with the catenins and the actin cytoskeleton. In human and in experimental cancers disturbance of the cadherin-catenin complex have been found at multiple levels. Candidate invasion-promoter molecules may be found among lytic enzymes and their associated molecules, motility factors and heterotypic cell-cell adhesion molecules. Investigation of the cellular interactions within the micro-ecosystem of bone metastasis has lead to the treatment of bone metastases with bisphosphonates. This application demonstrates the potential clinical benefit of a better understanding of the cellular and molecular mechanisms of cancer invasion and metastasis.
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PMID:[When and why does cancer metastasize? An overview of current viewpoints OF the molecular mechanism of invasiveness]. 804 67

Calcium-dependent cell-cell adhesion is mediated by the cadherin family of cell adhesion proteins. Transduction of cadherin adhesion into cellular reorganization is regulated by cytosolic proteins, termed alpha-, beta-, and gamma-catenin (plakoglobin), that bind to the cytoplasmic domain of cadherins and link them to the cytoskeleton. Previous studies of cadherin/catenin complex assembly and organization relied on the coimmunoprecipitation of the complex with cadherin antibodies, and were limited to the analysis of the Triton X-100 (TX-100)-soluble fraction of these proteins. These studies concluded that only one complex exists which contains cadherin and all of the catenins. We raised antibodies specific for each catenin to analyze each protein independent of its association with E-cadherin. Extracts of Madin-Darby canine kidney epithelial cells were sequentially immunoprecipitated and immunoblotted with each antibody, and the results showed that there were complexes of E-cadherin/alpha-catenin, and either beta-catenin or plakoglobin in the TX-100-soluble fraction. We analyzed the assembly of cadherin/catenin complexes in the TX-100-soluble fraction by [35S]methionine pulse-chase labeling, followed by sucrose density gradient fractionation of proteins. Immediately after synthesis, E-cadherin, beta-catenin, and plakoglobin cosedimented as complexes. alpha-Catenin was not associated with these complexes after synthesis, but a subpopulation of alpha-catenin joined the complex at a time coincident with the arrival of E-cadherin at the plasma membrane. The arrival of E-cadherin at the plasma membrane coincided with an increase in its insolubility in TX-100, but extraction of this insoluble pool with 1% SDS disrupted the cadherin/catenin complex. Therefore, to examine protein complex assembly in both the TX-100-soluble and -insoluble fractions, we used [35S]methionine labeling followed by chemical cross-linking before cell extraction. Analysis of cross-linked complexes from cells labeled to steady state indicates that, in addition to cadherin/catenin complexes, there were cadherin-independent pools of catenins present in both the TX-100-soluble and -insoluble fractions. Metabolic labeling followed by chase showed that immediately after synthesis, cadherin/beta-catenin, and cadherin/plakoglobin complexes were present in the TX-100-soluble fraction. Approximately 50% of complexes were titrated into the TX-100-insoluble fraction coincident with the arrival of the complexes at the plasma membrane and the assembly of alpha-catenin. Subsequently, > 90% of labeled cadherin, but no additional labeled catenin complexes, entered the TX-100-insoluble fraction.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Dynamics of cadherin/catenin complex formation: novel protein interactions and pathways of complex assembly. 820 61

The cadherins are a family of transmembrane glycoproteins responsible for calcium-dependent cell-cell adhesion. This adhesion is mediated by a group of cytoplasmic proteins, the catenins, which act inside the cell to couple the cadherin molecule to the microfilament cytoskeleton. Dysfunction of E-cadherin-dependent cell-cell adhesion has been demonstrated to contribute to the acquisition of invasive potential of malignant adenocarcinoma cells. The potential role of alterations of catenin expression in tumor cell invasion is largely unexplored. We have previously found that E-cadherin is frequently down-regulated in clinical samples of prostate cancer (Umbas, R., Schalken, J. A., Aalders, T. W., Carter, B. S., Karthaus, H. F. M., Schaafsma, H. E., Debruyne, F. M. J., and Isaacs, W. B. Cancer Res., 52: 5104-5109, 1992). In this study, we further investigate this adhesion system in both benign and malignant human prostate cells in culture. Using antibodies to E-cadherin and its cytoplasmic accessory protein, alpha-catenin, we find that 5 of 6 human prostate cancer cell lines have reduced or absent levels of one or the other or both of these molecules when compared to normal prostatic epithelial cells. Only the LNCaP prostate cancer cell line is indistinguishable from normal prostate epithelium with respect to its E-cadherin-alpha-catenin complement. Interestingly, the PC-3 line is characterized by the presence of E-cadherin, but the complete lack of alpha-catenin found at both the RNA and protein level. This lack of alpha-catenin gene expression is explained by Southern analysis, which reveals a homozygous deletion of a large portion of the alpha-catenin gene in PC-3 cells. This loss of alpha-catenin is functionally manifested by negligible Ca(2+)-dependent aggregation of these cells in vitro, when compared to LNCaP cells. These results confirm that E-cadherin-dependent cell-cell adhesion is frequently aberrant in prostate cancer cells, and suggest that in a subset of prostate cancers, this adhesion may be inactivated by loss of alpha-catenin rather than E-cadherin itself. Furthermore, these results demonstrate that mutational inactivation of the alpha-catenin gene is one mechanism responsible for the loss of normal cell-cell adhesion in prostate cancer.
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PMID:Reduction of E-cadherin levels and deletion of the alpha-catenin gene in human prostate cancer cells. 833 65

E- and P-cadherin are members of a family of calcium-dependent, cell surface glycoproteins involved in cell-cell adhesion. Extracellularly, the transmembrane cadherins self-associate, while intracellularly, they interact with the actin-based cytoskeleton. Several intracellular proteins, collectively termed catenins, are tightly associated with E- and P-cadherin. These proteins appear to link the cadherin to the cytoskeleton and have been proposed to be involved in concentrating cadherins at cell-cell adherens junctions. In this paper we report the production of monoclonal antibodies against both alpha- and beta-catenin and use these antibodies to show that in cells simultaneously expressing two different cadherins, E-cadherin and P-cadherin, each cadherin appears to be present in a separate cadherin/catenin complex.
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PMID:P- and E-cadherin are in separate complexes in cells expressing both cadherins. 834 78


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