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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In MDCK cells, presenilin-1 (PS1) accumulates at intercellular contacts where it colocalizes with components of the cadherin-based adherens junctions. PS1 fragments form complexes with E-cadherin, beta-catenin, and alpha-catenin, all components of adherens junctions. In confluent MDCK cells, PS1 forms complexes with cell surface E-cadherin; disruption of Ca(2+)-dependent cell-cell contacts reduces surface PS1 and the levels of PS1-E-cadherin complexes. PS1 overexpression in human kidney cells enhances cell-cell adhesion. Together, these data show that PS1 incorporates into the cadherin/catenin adhesion system and regulates cell-cell adhesion. PS1 concentrates at intercellular contacts in epithelial tissue; in brain, it forms complexes with both E- and N-cadherin and concentrates at synaptic adhesions. That PS1 is a constituent of the cadherin/catenin complex makes that complex a potential target for PS1 FAD mutations.
Mol Cell 1999 Dec
PMID:Presenilin-1 forms complexes with the cadherin/catenin cell-cell adhesion system and is recruited to intercellular and synaptic contacts. 1063 15

Despite the importance of epithelial cell contacts in determining cell behavior, we still lack a detailed understanding of the assembly and disassembly of intercellular contacts. Here we examined the role of the catalytic activity of the Src family kinases at epithelial cell contacts in vitro. Like E- and P-cadherin, Ca(2+) treatment of normal and tumor-derived human keratinocytes resulted in c-Yes (and c-Src and Fyn), as well as their putative substrate p120(CTN), being recruited to cell-cell contacts. A tyrosine kinase inhibitor with selectivity against the Src family kinases, PD162531, and a dominant-inhibitory c-Src protein that interferes with the catalytic function of the endogenous Src kinases induced cell-cell contact and E-cadherin redistribution, even in low Ca(2+), which does not normally support stable cell-cell adhesion. Time-lapse microscopy demonstrated that Src kinase inhibition induced stabilization of transiently formed intercellular contacts in low Ca(2+). Furthermore, a combination of E- and P-cadherin-specific antibodies suppressed cell-cell contact, indicating cadherin involvement. As a consequence of contact stabilization, normal cells were unable to dissociate from an epithelial sheet formed at high density and repair a wound in vitro, although individual cells were still motile. Thus, cadherin-dependent contacts can be stabilized both by high Ca(2+) and by inhibiting Src activity in low (0.03 mM) Ca(2+) in vitro.
Mol Biol Cell 2000 Jan
PMID:The catalytic activity of the Src family kinases is required to disrupt cadherin-dependent cell-cell contacts. 1063 90

The presence of cadherins, Ca(2+)-dependent cell-cell adhesion molecules which may be involved in gamete interaction, was investigated in human gametes. Expression of cadherin molecules was demonstrated using an anti-pan-cadherin antibody and specific antibodies against the three classical cadherins: E- (epithelial), P- (placental) and N- (neural) cadherins. Samples of 48 h old unfertilized oocytes and spermatozoa from in-vitro fertilizing semen samples were lysed and separated by electrophoresis. Localization of cadherins was determined on intact, fixed, permeabilized spermatozoa and oocytes by immunocytochemisty assessed by confocal microscopy. Immunoblotting with the pan-cadherin antibody revealed a single band of approximately 120 kDa in spermatozoa (whether 'fresh', capacitated, or frozen-thawed) and oocyte extracts. Oocytes presented all three classical cadherins with the appropriate molecular weights of 120-130 kDa. In sperm lysate we demonstrated the presence of E-cadherin but not N-cadherin. The anti-P antibody detected a 90 kDa peptide as the only immunoreactive antigen. Following immunocytochemistry of human oocytes all cadherin molecules were allocated predominantly to the plasma membrane with only traces in the cytoplasm. In spermatozoa, several staining patterns were observed with each of the pan-cadherin, N-cadherin and E-cadherin antibodies mostly confined to different head regions. We conclude that cadherin molecules are present on plasma membranes of both human spermatozoa and oocytes and may play a role in the intricate recognition process preceding gamete fusion.
Mol Hum Reprod 2000 Feb
PMID:Expression of cadherin adhesion molecules on human gametes. 1065 58

2-Amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), a compound found in cooked meat, is a mammary gland carcinogen in female Sprague-Dawley rats. PhIP-induced rat mammary gland carcinomas were examined for mutations in several genes (exons) known to regulate cell growth and apoptosis, including p53 (4-8), p21(Waf1) (coding region), Apc (14, 15), B-catenin (3), E-cadherin (9,13,15), Bcl-x (coding region), Bax (3), IGFIIR (28), and TGFBIIR (3). DNA from 30 carcinomas was examined by single-strand conformation polymorphism analysis, but no mutations were detected in these genes or gene regions. DNA from carcinomas and matching normal tissue were further screened for allelic imbalance by using a polymerase chain reaction-based approach with primers to known microsatellite regions located throughout the rat genome. Of 53 markers examined, 12 revealed allelic imbalance. Microsatellite instability (MSI) was detected at two markers, one on chromosome 4 and one on chromosome 6. Sixty-five percent and 96% of all carcinomas examined (N=23) showed MSI at these loci on chromosomes 4 and 6, respectively, supporting the notion that MSI plays a role in PhIP-induced mammary carcinogenesis. Loss of heterozygosity (LOH), an indication of a possible tumor suppressor gene, was observed at 10 markers distributed on chromosomes 3, 10, 11, 14, and X. The frequency of LOH at these markers was 75-94%, supporting that the regions of allelic imbalance were largely similar for the PhIP-induced carcinomas examined in this study. When PhIP-induced carcinomas from rats placed on high-fat and low-fat diet were compared, no unique regions of allelic imbalance or statistical differences in the frequency of allelic imbalance were observed. Therefore, the high-fat diet, known to be a promoter of PhIP-induced rat mammary carcinogenesis, did not appear to influence allelic imbalance in the carcinomas. Interestingly, 7,12-dimethylbenz[a]-anthracene-induced mammary carcinomas did not show allelic imbalance at 11 of the 12 loci that showed allelic imbalance in PhIP-induced carcinomas. These findings suggest that distinct chemical carcinogens induce different patterns of allelic imbalance during rat mammary carcinogenesis. Since several of the known genes involved in carcinogenesis did not harbor mutations in PhIP-induced carcinomas, further studies are needed to clarify the critical genes involved in PhIP-induced mammary carcinogenesis and to determine whether regions of LOH harbor potentially novel tumor suppressor genes involved in this disease.
Mol Carcinog 2000 Feb
PMID:Genomic imbalance in rat mammary gland carcinomas induced by 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine. 1065

The topographical organisation of the epithelium lining mucous membranes has been an intense point of research. One of the fundamental biological issues underpinning this and associated issues relates to the role and regulation of epithelial adhesion molecules. Adhesion between individual cells allows an intact layer to be formed, which is selectively permeable. In addition, the orchestrated regulation of multiple adhesion molecules allows the gradual transition from basal secretory cells to apical absorptive cells in the crypt-villus gradient. Moreover, it is becoming clear that no one class of adhesion molecule can sufficiently govern crypt architecture; however, the main cell-cell adhesion molecules are the cadherins and the related desmosomal cadherins. These latter molecules interact with the catenins, which bind directly or indirectly with cytoskeletal molecules such as Rho and Rac. In addition, other complex glycoproteins, such as the carcinoembryonic antigens, might contribute to adhesion, although their mechanisms of function are distinctly different. Integrins on the basal aspect of the cells also signal important morphoregulatory signals as a result of their binding to the extracellular maxtrix. The disruption of these physiological processes also provides a necessary and, in some cases, sufficient molecular mechanism for cancer invasion and metastasis, such as occurs in E-cadherin mutation positive familial gastric cancer.
Mol Pathol 1999 Aug
PMID:Cadherin adhesion in the intestinal crypt regulates morphogenesis, mitogenesis, motogenesis, and metaplasia formation. 1069 34

The ability of tumours to metastasis is regarded as one of the hallmarks of malignancy. The process through which tumours evolve to achieve this has been termed the metastatic cascade. This cascade has been the subject of much investigation over many years. One of the vital events identified by these investigations is the reduction of adhesion between tumour cells facilitating invasion of the surrounding tissues and vascular channels, ultimately leading to the development of a distant metastasis. E-cadherin and its associated catenin complex have been identified as key molecules in cell adhesion. This review looks at the structure and interaction of the E-cadherin-catenin complex and the factors that appear to regulate E-cadherin expression and thus cell adhesion. From the data gathered, it has become possible to propose the hypothesis that the development of tumour hypoxia is the initiating factor that sets the tumour on the road to metastasis.
Mol Pathol 1999 Aug
PMID:Regulation of E-cadherin: does hypoxia initiate the metastatic cascade? 1069 37

alpha E beta 7 is a member of the integrin family and is expressed almost exclusively by cells of the T lymphocyte lineage in mucosal tissues. Expression is induced by transforming growth factor beta in the mucosal microenvironment. Genetic elements that control transcription are under investigation and may prove valuable for directing the expression of transgenes in mucosal T cells. The only known ligand for alpha E beta 7 is E-cadherin, which is expressed on epithelial cells. In this article, molecular aspects of ligand recognition by alpha E beta 7 in relation to recent structural data on cadherin domains are reviewed. Expression of alpha E beta 7 is often increased in inflammatory diseases, particularly where T cells infiltrate epithelial tissues. The function of alpha E beta 7 is not yet fully understood, but it is likely to be important in retention of T cells in mucosal tissues and may also have a role in cell signalling and communication between lymphocytes and epithelial surfaces.
Mol Pathol 1999 Aug
PMID:Alpha E beta 7. 1069 40

In the Madin-Darby canine kidney epithelial cell line, the proteins occludin and ZO-1 are structural components of the tight junctions that seal the paracellular spaces between the cells and contribute to the epithelial barrier function. In Ras-transformed Madin-Darby canine kidney cells, occludin, claudin-1, and ZO-1 were absent from cell-cell contacts but were present in the cytoplasm, and the adherens junction protein E-cadherin was weakly expressed. After treatment of the Ras-transformed cells with the mitogen-activated protein kinase kinase (MEK1) inhibitor PD98059, which blocks the activation of mitogen-activated protein kinase (MAPK), occludin, claudin-1, and ZO-1 were recruited to the cell membrane, tight junctions were assembled, and E-cadherin protein expression was induced. Although it is generally believed that E-cadherin-mediated cell-cell adhesion is required for tight junction assembly, the recruitment of occludin to the cell-cell contact area and the restoration of epithelial cell morphology preceded the appearance of E-cadherin at cell-cell contacts. Both electron microscopy and a fourfold increase in the transepithelial electrical resistance indicated the formation of functional tight junctions after MEK1 inhibition. Moreover, inhibition of MAPK activity stabilized occludin and ZO-1 by differentially increasing their half-lives. We also found that during the process of tight junction assembly after MEK1 inhibition, tyrosine phosphorylation of occludin and ZO-1, but not claudin-1, increased significantly. Our study demonstrates that down-regulation of the MAPK signaling pathway causes the restoration of epithelial cell morphology and the assembly of tight junctions in Ras-transformed epithelial cells and that tyrosine phosphorylation of occludin and ZO-1 may play a role in some aspects of tight junction formation.
Mol Biol Cell 2000 Mar
PMID:Restoration of tight junction structure and barrier function by down-regulation of the mitogen-activated protein kinase pathway in ras-transformed Madin-Darby canine kidney cells. 1071 4

E-cadherin (uvomorulin)-mediated cell interactions are essential for preimplantation development in mammals. We observed that E-cadherin is expressed at contact sites between blastomeres of 2-cell mouse embryos of non-blocking genotype (CBA x C57BL F1) explanted at 32 h post human chorionic gonadotrophin (HCG) and cultured in vitro, while blastomere rounding and reduced zones of contact and E-cadherin-staining were observed in embryos of a blocking strain (MF1) arrested at the 2-cell stage. Embryos of MF1 strain can be rescued by aggregation with four 2-cell embryos of the non-blocking genotype. An early event in rescue is E-cadherin expression at contact zones between adjacent embryos of different genotype in aggregation chimeras. E-cadherin-mediated signalling appears important for the rescue (including formation of adherens-like contacts, cell polarization and morphogenetic processes) since there is no rescue when E-cadherin-specific antibodies are present during phytohaemagglutinin-mediated aggregation and subsequent culture. In blocked embryos, the distribution of microtubules is disturbed and concomitantly mitochondria cluster around the nucleus. Rescue by aggregation retains normal mitochondrial distribution in the presence of a dense microtubular lattice in all blastomeres. Therefore, E-cadherin-mediated signalling and its downstream effects on cytoskeletal organization are essential in the rescue of blocking embryos by aggregation. Normal preimplantation development appears to be dependent on the polarized expression of surface E-cadherin and the microtubule-mediated dispersal of mitochondria.
Mol Hum Reprod 2000 May
PMID:Surface-expressed E-cadherin, and mitochondrial and microtubule distribution in rescue of mouse embryos from 2-cell block by aggregation. 1077 50

To determine how histamine regulates endothelial barrier function through an integrative cytoskeletal network, we mathematically modeled the resistance across an endothelial cell-covered electrode as a function of cell-cell, cell-matrix, and transcellular resistances. Based on this approach, histamine initiated a rapid decrease in transendothelial resistance predominantly through decreases in cell-cell resistance in confluent cultured human umbilical vein endothelial cells (HUVECs). Restoration of resistance was characterized by initially increasing cell-matrix resistance, with later increases in cell-cell resistance. Thus histamine disrupts barrier function by specifically disrupting cell-cell adhesion and restores barrier function in part through direct effects on cell-matrix adhesion. To validate the precision of our technique, histamine increased the resistance in subconfluent HUVECs in which there was no cell-cell contact. Exposure of confluent monolayers to an antibody against cadherin-5 caused a predominant decrease in cell-cell resistance, whereas the resistance was unaffected by the antibody to cadherin-5 in subconfluent cells. Furthermore, we observed an increase predominantly in cell-cell resistance in ECV304 cells that were transfected with a plasmid containing a glucocorticoid-inducible promoter controlling expression of E-cadherin. Transmission electron microscopy confirmed tens of nanometer displacements between adjacent cells at a time point in which histamine maximally decreased cell-cell resistance.
Am J Physiol Lung Cell Mol Physiol 2000 May
PMID:Histamine alters endothelial barrier function at cell-cell and cell-matrix sites. 1078 18


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