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)

Cadherins represent a gene family of Ca(2+)-dependent cell adhesion molecules (CAMs) identified during development and in adult organs. They generally mediate cell-cell adhesion by homotypic interaction, although heterotypic binding between different cadherin molecules is possible. Molecular cloning and sequence comparison has led to the characterization of a highly homologous group of 'classical' cadherins and more distantly related members, together composing a gene superfamily. The classical cadherins are transmembrane glycoproteins which exhibit, in addition to the structural homologies, a very similar overall protein topology. Protein sequence comparison has led to the identification of domains of common functional importance. The cytoplasmic domains of cadherins associate with peripheral cytoplasmic proteins termed catenin alpha, beta and gamma with molecular weights of 102, 88 and 80 kDa respectively. This complex formation seems to regulate the adhesive function of cadherins, most likely by connecting cadherins with actin microfilaments. Possible implications of catenins for cadherin function are discussed.
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PMID:Classical cadherins. 162 4

The cytoplasmic region of the Ca(2+)-dependent cell-adhesion molecule (CAM) uvomorulin associates with distinct cytoplasmic proteins with molecular masses of 102, 88, and 80 kDa termed alpha, beta, and gamma catenin, respectively. This complex formation links uvomorulin to the actin filament network, which seems to be of primary importance for its cell-adhesion properties. We show here that antibodies against alpha catenin also immunoprecipitate complexes that contain human N-cadherin, mouse P-cadherin, chicken A-CAM (adherens junction-specific CAM; also called N-cadherin) or Xenopus U-cadherin, demonstrating that alpha catenin is complexed with other cadherins. In immunofluorescence tests, alpha catenin is colocalized with cadherins at the plasma membrane. However, in cadherin-negative Ltk- cells, alpha catenin is found uniformly distributed in the cytoplasm, suggesting some additional biological function(s). Expression of uvomorulin in these cells results in a concentration of alpha catenin at membrane areas of cell contacts. We also have cloned and sequenced murine alpha catenin. The deduced amino acid sequence reveals a significant homology to vinculin. Our results suggest the possibility of a new vinculin-related protein family involved in the cytoplasmic anchorage of cell-cell and cell-substrate adhesion molecules.
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PMID:The uvomorulin-anchorage protein alpha catenin is a vinculin homologue. 192 79

We have recently found that the cytoplasmic region of the cell adhesion molecule uvomorulin associates with three proteins named catenin alpha, beta, and gamma. Here we show by analysis of various mutant uvomorulin polypeptides expressed in mouse L cells that this association is mediated by a specific domain in the cytoplasmic region. A specific recognition site for catenins is located in a 72-amino acid domain. Interestingly, 69 of the 72 amino acid residues are encoded by a single exon of the uvomorulin gene. To demonstrate the direct interaction between catenins and the 72-amino acid domain, cDNA constructs composed of H-2Kd cDNA and various 3' sequences of uvomorulin were expressed in L cells. Chimeric proteins between H-2Kd and the 72-amino acid domain of uvomorulin were shown, by immunoprecipitation with anti-H-2Kd antibodies, to complex with catenin alpha, beta, and gamma. Catenins connect uvomorulin to cytoskeletal structures. We provide biochemical evidence for an association of the uvomorulin-catenin complex with actin bundles. Our results suggest that catenin alpha plays a key role in the association with actin filaments, whereas catenin beta binds more directly to the cytoplasmic region of uvomorulin. In cell aggregation assays with transfected cells expressing normal or mutant uvomorulin, the adhesive function was expressed only when uvomorulin was associated with catenins. From these results we conclude that the cytoplasmic anchorage of uvomorulin is of major biological importance.
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PMID:Uvomorulin-catenin complex formation is regulated by a specific domain in the cytoplasmic region of the cell adhesion molecule. 234 35

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

At least three proteins (alpha, beta, and gamma catenin) comprise the cytoplasmic domain of the cadherin cell-cell adhesion complex. We have cloned and sequenced human epithelial alpha(E)-catenin and have identified two distinct transcripts, designated alpha 1- and alpha 2-. The human alpha 1(E)-catenin transcript predicts a 907 aa sequence 97% identical to mouse alpha-catenin. The second transcript, alpha 2(E)-catenin, displays a 24 amino acid insertion after codon 812, yielding a 931 amino acid protein (GenBank #L23805). Analysis by RT-PCR and Northern blotting detects one or both transcripts in epithelial and non-epithelial tissues. Southern blotting indicates that both arise from a single gene. The alternative transcription site in alpha-catenin is analogous to the splice site in vinculin that creates met alpha-vinculin, extending the homology between alpha-catenin and vinculin. These data with the reported structure of other catenin genes suggest that vinculin and alpha-catenin generate a superfamily of proteins mediating membrane-cytoskeletal associations.
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PMID:Molecular cloning reveals alternative splice forms of human alpha(E)-catenin. 794 18

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 Ca(2+)-dependent intercellular adhesion molecule cadherin is known to be linked to the cytoskeleton by the protein catenin, an association of which appears to be important for the cell-adhesion function of cadherin. Catenin consists of three subtypes-alpha, beta, and gamma. In our previous study, N-cadherin was shown to be localized on the plasmalemma of normal and regenerating chick peripheral nerve. Thus, as alpha N-catenin is a subtype of alpha-catenin (which is specifically associated with N-cadherin), we investigated the immunolocalization of alpha N-catenin in normal and regenerating chick sciatic nerve. In normal nerve, unmyelinated axons exhibited either intense or weak alpha N-catenin immunoreactivity throughout the axoplasm, whereas myelinated axons were completely immunonegative. Regenerating axons, including those derived from parent myelinated axons, showed alpha N-catenin immunoreactivity of variable intensities in growth cones and axon shafts. Schwann cells were invariably devoid of immunoreactivity. Thus alpha N-catenin is not necessarily bound to the surface plasmalemma, but is distributed throughout the cytoplasm, suggesting that most alpha N-catenin molecules are dissociated from N-cadherin.
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PMID:Alpha N-catenin expression in the normal and regenerating chick sciatic nerve. 901 23

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

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

Dysfunction of the cadherin-catenin complex, a key component of adherens junctions, is thought to confer invasive potential to cells. The aim of this study is to examine the expression and function of the E-cadherin/catenin complex in gastric carcinoma cell lines. Expression of E-cadherin, alpha, beta and gamma-catenin and p120ctn, and of the adenomatous polyposis coli protein (APC), together with function of the cadherin-catenin complex was examined in a panel of gastric carcinoma cell lines, using immunocytochemistry, Western blotting and a cell-cell aggregation assay. Protein interactions were examined by sequential immunoprecipitation and immunoblotting with antibodies to E-cadherin, alpha, beta and gamma-catenin, p120ctn and APC. Abnormalities of E-cadherin, alpha- and beta-catenin expression, were associated with disturbance of E-cadherin-catenin complex composition, loss of membranous localization and loss of calcium-dependent aggregation in six gastric carcinoma cell lines. APC protein expression and interaction with beta-catenin was preserved in five cell lines. We demonstrate frequent abnormalities of expression and function of E-cadherin and catenins, and associated disturbance of E-cadherin-mediated intercellular adhesion in gastric carcinoma cell lines. These findings support the tumour suppressor role of the E-cadherin and its contribution to the development and progression of the neoplastic phenotype in gastric carcinoma.
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PMID:Abnormal expression and function of the E-cadherin-catenin complex in gastric carcinoma cell lines. 1040 33


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