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

Catenins were first characterized as linking the cytoplasmic domains of cadherin cell-cell adhesion molecules to the cortical actin cytoskeleton. In addition to their essential role in modulating cadherin adhesivity, catenins have more recently been indicated to participate in cell and developmental signaling pathways. beta-Catenin, for example, associates directly with at least two receptor tyrosine kinases and transduces developmental signals within the Wnt pathway. Catenins also complex with the tumor suppressor protein adenomatous polyposis coli (APC), which appears to have a role in regulating cell proliferation. We have used the yeast two-hybrid method to reveal that fascin, a bundler of actin filaments, binds to beta-catenin's central Armadillo repeat domain. Western blotting of immunoprecipitates from cell line and mouse and rat brain extracts indicate that this interaction exists in vivo. Fascin and beta-catenin's association was further substantiated in vitro using purified proteins isolated from recombinant bacterial and baculoviral sources. Immunoprecipitation analysis indicates that fascin additionally binds to plakoglobin, which is highly homologous to beta-catenin but not to p120cas, a newly described catenin which contains a more divergent Armadillo-repeat domain. Immunoprecipitation, in vitro competition, and domain-mapping experiments demonstrate that fascin and E-cadherin utilize a similar binding site within beta-catenin, such that they form mutually exclusive complexes with beta-catenin. Immunofluorescence microscopy reveals that fascin and beta-catenin colocalize at cell-cell borders and dynamic cell leading edges of epithelial and endothelial cells. In addition to cell-cell borders, cadherins were unexpectedly observed to colocalize with fascin and beta-catenin at cell leading edges. It is conceivable that beta-catenin participates in modulating cytoskeletal dynamics in association with the microfilament-bundling protein fascin, perhaps in a coordinate manner with its functions in cadherin and APC complexes.
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PMID:beta-Catenin associates with the actin-bundling protein fascin in a noncadherin complex. 879 67

Loss of E-cadherin-mediated adhesion is an important step in the progression of many carcinomas. In model systems, it has been shown that cadherin function requires not only proper E-cadherin expression but also its linkage to the cytoskeleton through catenins. Hence, defects in catenins may cause defective E-cadherin function, and catenins as well as E-cadherin might constitute prognostic indicators. Here, we extend our previous study on E-cadherin in bladder cancer (Cancer Res., 53: 3241-3245, 1993). We have evaluated the expression of E-cadherin-associated cytoplasmic molecules (alpha-, beta-, and gamma-catenins and p120cas) to clarify whether or not the pattern of their expression could provide additional prognostic information beyond that from E-cadherin alone. Forty-eight frozen bladder tumor specimens and 9 samples of normal urothelium were studied by immunohistochemistry. A discrepancy between the E-cadherin and catenin expression pattern was seen in 20.8% of cases. Abnormal expression of each molecule is significantly correlated with tumor grade (P < 0.01) and stage (P < 0.01). Reduced expression of all of the molecules correlates with poor survival (P < 0.01 for each variable). Proportional hazard regression analysis showed that beta-catenin, E-cadherin, and alpha-catenin have strong predictive value, whereas plakoglobin and p120cas have a somewhat lower predictive value. Within patients with invasive tumors, those with a normal staining for either E-cadherin, alpha-catenin, or beta-catenin show a trend toward better survival. However, the difference in survival is significant only for E-cadherin (P < 0.05). Thus, beta-catenin, E-cadherin, and alpha-catenin have similar prognostic values. Therefore, from a practical point of view, the expression of any of these proteins can be of prognostic value for patients with bladder cancer.
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PMID:Prognostic value of cadherin-associated molecules (alpha-, beta-, and gamma-catenins and p120cas) in bladder tumors. 879 85

Cadherins comprise a family of calcium-dependent glycoproteins that function in mediating cell-cell adhesion in virtually all solid tissues of multicellular organisms. In epithelial cells, E-cadherin represents a key molecule in the establishment and stabilization of cellular junctions. On the cellular level, E-cadherin is concentrated at the adherens junction and interacts homophilically with E-cadherin molecules of adjacent cells. Significant progress has been made in understanding the extra- and intracellular interactions of E-cadherin. Recent success in solving the three-dimensional structure of an extracellular cadherin domain provides a structural basis for understanding the homophilic interaction mechanism and the calcium requirement of cadherins. According to the crystal structure, individual cadherin molecules cooperate to form a linear cell adhesion zipper. The intracellular anchorage of cadherins is regulated by the dynamic association with cytoplasmic proteins, termed catenins. The cytoplasmic domain of E-cadherin is complexed with either beta-catenin or plakoglobin (gamma-catenin). Beta-catenin and plakoglobin bind directly to alpha-catenin, giving rise to two distinct cadherin-catenin complexes (CCC). Alpha-catenin is thought to link both CCC's to actin filaments. The anchorage of cadherins to the cytoskeleton appears to be regulated by tyrosine phosphorylation. Phosphorylation-induced junctional disassembly targets the catenins, indicating that catenins are components of signal transduction pathways. The unexpected association of catenins with the product of the tumor suppressor gene APC has led to the discovery of a second, cadherin-independent catenin complex. Two separate catenin complexes are therefore involved in the cross-talk between cell adhesion and signal transduction. In this review we focus on protein interactions regulating the molecular architecture and function of the CCC. In the light of a fundamental role of the CCC during mammalian development and tissue morphogenesis, we also discuss the phenotypes of embryos lacking E-cadherin or beta-catenin.
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PMID:Cadherin-catenin complex: protein interactions and their implications for cadherin function. 880 74

The p120cas gene encodes a protein tyrosine kinase substrate that associates with the cell-cell adhesion protein complex containing E-cadherin and its cytoplasmic cofactors alpha-catenin, beta-catenin, and plakoglobin. Like other components of the cadherin/catenin complex, defects in p120cas may contribute to cell malignancy. We have determined the chromosomal location of the p120cas gene in human and mouse using fluorescence in situ hybridization and interspecific backcross analysis, respectively. The human p120cas gene (CTNND) is localized immediately adjacent to the centromere on the long arm of chromosome 11 in band 11q11. The murine p120cas gene (Catns) was assigned to the middle of chromosome 2. Neither locus is currently known to be associated with disease or malignancy.
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PMID:The gene encoding p120cas, a novel catenin, localizes on human chromosome 11q11 (CTNND) and mouse chromosome 2 (Catns). 880 91

RPTP mu is a receptor-like protein tyrosine phosphatase that mediates homophilic cell-cell interactions. Surface expression of RPTP mu is restricted to cell-cell contacts and is upregulated with increasing cell density, suggesting a role for RPTP mu in contact-mediated signaling. It was recently reported (Brady-Kalnay, S.M., D.L. Rimm, and N.K. Tonks. 1995. J. Cell Biol. 130:977-986) that RPTP mu binds directly to cadherin/catenin complexes, and thus may regulate the tyrosine phosphorylation of such complexes. Here we report that this concept needs revision. Through reciprocal precipitations using a variety of antibodies against RPTP mu, cadherins, and catenins, we show that RPTP mu does not interact with cadherin/catenin complexes, even when assayed under very mild lysis conditions. We find that the anti-RPTP mu antiserum used by others precipitates cadherins in a nonspecific manner independent of RPTP mu. We conclude that, contrary to previous claims, RPTP mu does not interact with cadherin complexes and thus is unlikely to directly regulate cadherin/catenin function.
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PMID:Lack of association between receptor protein tyrosine phosphatase RPTP mu and cadherins. 883 Jul 78

Cadherins are calcium-dependent cell adhesion molecules that play fundamental roles in embryonic development, tissue morphogenesis, and cancer. A prerequisite for their function is association with the actin cytoskeleton via the catenins. Tyrosine phosphorylation of beta-catenin, which correlates with a reduction in cadherin-dependent cell adhesion, may provide cells with a mechanism to regulate cadherin activity. Here we report that beta-catenin immune precipitates from PC12 cells contain tyrosine phosphatase activity which dephosphorylates beta-catenin in vitro. In addition, we show that a member of the leukocyte antigen-related protein (LAR)-related transmembrane tyrosine phosphatase family (LAR-PTP) associates with the cadherin-catenin complex. This association required the amino-terminal domain of beta-catenin but does not require the armadillo repeats, which mediate association with cadherins. The interaction also is detected in PC9 cells, which lack alpha-catenin. Thus, the association is not mediated by alpha-catenin or by cadherins. Interestingly, LAR-PTPs are phosphorylated on tyrosine in a TrkA-dependent manner, and their association with the cadherin-catenin complex is reduced in cells treated with NGF. We propose that changes in tyrosine phosphorylation of beta-catenin mediated by TrkA and LAR-PTPs control cadherin adhesive function during processes such as neurite outgrowth.
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PMID:Association between a transmembrane protein tyrosine phosphatase and the cadherin-catenin complex. 883 Jul 79

We have studied transcription, expression, and membrane localization of components of the E-cadherin-catenin complex stage by stage during mouse preimplantation development. Maternal E-cadherin and alpha- and beta-catenin are stored as mRNA and/or protein in unfertilized eggs and are already assembled into a protein complex at this stage. After fertilization, it is likely that they mediate adhesion of early-stage blastomeres. Biosynthesis of plakoglobin is delayed relative to the other components. The temporal mRNA and protein expression patterns of the components of the cadherin-catenin complex correlate with the presence or absence of potential cytoplasmic polyadenylation elements (CPEs) in the 3'-UTRs of the respective cDNAs. Our results suggest that the components of the E-cadherin-catenin complex derived from both maternal and zygotic gene activity are increasingly accumulated and stored in a nonfunctional form during early cleavage stages and are ready to be used for compaction and the formation of the trophectodermal cell layer.
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PMID:Expression and cell membrane localization of catenins during mouse preimplantation development. 885 88

The Wnt genes encode secreted glycoproteins used in intercellular communication at multiple steps during development. Signalling by Wingless, the Drosophila Wnt-1 homologue, requires the activity of Armadillo, the homologue of vertebrate beta-catenin, which is a component of the cadherin/catenin complex at adherens junctions. The genetic link between wingless and armadillo suggests that cell fate specification and cell-cell adhesion might be controlled concurrently. For instance, in one extreme view, Wingless could specify cell fate entirely by modulating cell adhesion. Alternatively, it might signal independently of adherens junctions. To distinguish between these alternatives, we have expressed two polypeptides that have opposite effects on cadherin-dependent adhesion: full-length Drosophila E-cadherin and a dominant-negative truncated form. We found that overexpression of either construct mimics wingless phenotypes, thereby uncoupling changes in adhesion from signalling effects. We demonstrate that both constructs titrate Armadillo from a 'signalling' pool which is functionally distinct from the junctional pool.
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PMID:Uncoupling cadherin-based adhesion from wingless signalling in Drosophila. 885 39

Polymorphonuclear leukocytes (PMN) infiltration into tissues is frequently accompanied by increase in vascular permeability. This suggests that PMN adhesion and transmigration could trigger modifications in the architecture of endothelial cell-to-cell junctions. In the present paper, using indirect immunofluorescence, we found that PMN adhesion to tumor necrosis factor-activated endothelial cells (EC) induced the disappearance from endothelial cell-to-cell contacts of adherens junction (AJ) components: vascular endothelial (VE)-cadherin, alpha-catenin, beta-catenin, and plakoglobin. Immunoprecipitation and Western blot analysis of the VE-cadherin/catenin complex showed that the amount of beta-catenin and plakoglobin was markedly reduced from the complex and from total cell extracts. In contrast, VE-cadherin and alpha-catenin were only partially affected. Disorganization of endothelial AJ by PMN was not accompanied by EC retraction or injury and was specific for VE-cadherin/catenin complex, since platelet/endothelial cell adhesion molecule 1 (PECAM-1) distribution at cellular contacts was unchanged. PMN adhesion to EC seems to be a prerequisite for VE-cadherin/catenin complex disorganization. This phenomenon could be fully inhibited by blocking PMN adhesion with an anti-integrin beta 2 mAb, while it could be reproduced by any condition that induced increase of PMN adhesion, such as addition of PMA or an anti-beta 2-activating mAb. The effect on endothelial AJ was specific for PMN since adherent activated lymphocytes did not induce similar changes. High concentrations of protease inhibitors and oxygen metabolite scavengers were unable to prevent AJ disorganization mediated by PMN. PMN adhesion to EC was accompanied by increase in EC permeability in vitro. This effect was dependent on PMN adhesion, was not mediated by proteases and oxygen-reactive metabolites, and could be reproduced by EC treatment with EGTA. Finally, immunohistochemical analysis showed that VE-cadherin distribution was affected by PMN adhesion to the vessel wall in vivo too. This work suggests that PMN adhesion could trigger intracellular signals in EC that possibly regulate VE-cadherin /catenin complex disorganization. This effect could increase EC permeability and facilitate PMN transmigration during the acute inflammatory reaction.
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PMID:Polymorphonuclear leukocyte adhesion triggers the disorganization of endothelial cell-to-cell adherens junctions. 889 5

The cadherin gene superfamily of calcium-dependent cell-cell adhesion molecules contains more than 40 members. We summarize functions attributed to these proteins, especially their roles in cellular differentiation and embryogenesis. We also describe hierarchies of protein-protein interactions between cadherins and cadherin-associated proteins (catenins). Several signal transduction pathways converge on, and diverge from, the cadherin/catenin complex to regulate its function; we speculate on roles of these signaling processes for cell structure and function. This review provides a framework for interpretation of developmental functions of cadherin cell adhesion molecules.
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PMID:Cadherin cell adhesion molecules in differentiation and embryogenesis. 890 Sep 59


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