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

The FER gene encodes a cytoplasmic tyrosine kinase with a single SH2 domain and an extensive amino terminus. In order to understand the cellular function of the FER kinase, we analyzed the effect of growth factor stimulation on the phosphorylation and activity of FER. Stimulation of A431 cells and 3T3 fibroblasts with epidermal growth factor or platelet-derived growth factor results in the phosphorylation of FER and two associated polypeptides. The associated polypeptides were shown to be the epidermal growth factor receptor or the platelet-derived growth factor receptor and a previously identified target, pp120. Since pp120 had previously been shown to interact with components of the cadherin-catenin complex, these results implicate FER in the regulation of cell-cell interactions. The physical association of FER with pp120 was found to be constitutive and was mediated by a 400-amino-acid sequence in the amino terminus of FER. Analyses of that sequence revealed that it has the ability to form coiled coils and that it oligomerizes in vitro. The identification of a coiled coil sequence in the FER kinase and the demonstration that the sequence mediates association with a potential substrate suggest a novel mechanism for signal transduction by cytoplasmic tyrosine kinases.
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PMID:The cytoplasmic tyrosine kinase FER is associated with the catenin-like substrate pp120 and is activated by growth factors. 762 46

The effect of hepatocyte growth factor/scatter factor (HGF/SF) and epidermal growth factor (EGF) on cadherin-mediated adhesion of human carcinoma cells was studied. HGF/SF induced scattering of colonic adenocarcinoma HT29 and gastric adenocarcinomas MKN7 and MKN74 cells. Likewise, EGF induced scattering of HT29 and MKN7 cells. These cells expressed E-cadherin, which was concentrated at cell-cell contact sites. When the scattering of these cells was induced by HGF/SF or EGF, the E-cadherin concentration at cell-cell boundaries tended to decrease. Immunoblotting analyses, however, demonstrated that these growth factor treatments did not alter the expression of E-cadherin and E-cadherin-associated proteins, alpha- and beta-catenin and plakoglobin. beta-Catenin, plakoglobin and an unidentified 115-kDa molecule associated with E-cadherin were found to be phosphorylated at tyrosine residues, and these phosphorylations were enhanced by the growth factor treatments. These results suggest that HGF/SF and EGF may modulate the function of the cadherin-catenin system via tyrosine phosphorylation of cadherin-associated proteins.
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PMID:Tyrosine phosphorylation of beta-catenin and plakoglobin enhanced by hepatocyte growth factor and epidermal growth factor in human carcinoma cells. 808 83

Various types of tumors show aberrant expression and overexpression of epidermal growth factor (EGF) receptor and the degree of receptor expression correlates with a malignant phenotype in many epithelial tumors. However, in vitro evidence supporting the advantageous role of receptor overexpression is deficient. In this study, we compared the effects of exogenous EGF on the cell colony morphology in monolayer and collagen gel culture between HSC-1 squamous carcinoma cells overexpressing EGF receptor and their revertant subline cells. These cells formed coherent cell colonies under routine culture conditions, but addition of EGF induced dissociation of cell colonies within 24 h in the parent HSC-1 cells, though not in the subline cells. Since the colony dissociation apparently involved loss of cell-cell adhesion, we also studied the effects of EGF on E-cadherin expression and its function. Cell aggregation assays showed that EGF reduced E-cadherin function dose-dependently in the parent cells, but not in the subline cells. However, immunoblotting analysis and ELISA showed the absence of downregulation or degradation of E-cadherin. Instead, EGF tyrosine phosphorylated cadherin/catenin complex components including beta-catenin and increased the detergent solubility of E-cadherin in the parent cells. These results suggest that EGF modified the functional association between E-cadherin and actin filament through tyrosine phosphorylation of the cadherin/catenin complex and thereby made the adhesion molecule incompetent. Our results indicate that the ligand activation of overexpressed EGF receptor impairs E-cadherin-mediated cell-cell adhesion and causes dissociation of the squamous carcinoma cell colonies, which facilitates tumor cell invasion in vivo. This might be relevant to the advantageous role of EGF receptor overexpression in malignant phenotype of epithelial tumor cells.
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PMID:Ligand activation of overexpressed epidermal growth factor receptor results in colony dissociation and disturbed E-cadherin function in HSC-1 human cutaneous squamous carcinoma cells. 863 95

Alterations in the expression or function of molecules that affect cellular adhesion and proliferation are thought to be critical events for tumor progression. Loss of expression of the cell adhesion molecule E-cadherin and increased expression of the epidermal growth factor receptor are two prominent molecular events that are associated with tumorigenesis. The regulation of E-cadherin-dependent cell adhesion by epidermal growth factor (EGF) was therefore examined in the human breast cancer cell line, MDA-MB-468. In this study, changes were observed in the subcellular distribution of components that mediate the cytoplasmic connection between E-cadherin and the actin-based cytoskeleton in response to activation of the EGF receptor. Serum withdrawal activated E-cadherin-dependent cell-cell aggregation in MDA-MB-468 cells, and this treatment stimulated the interaction of actin, alpha-actinin, and vinculin with E-cadherin complexes, despite the absence of alpha-catenin in these cells. By contrast, the co-precipitation of actin with E-cadherin was not detected in several alpha-catenin positive epithelial cell lines. Treatment with EGF inhibited cellular aggregation but did not affect either the levels of E-cadherin or catenin expression nor the association of catenins (beta-catenin, plakoglobin/gamma-catenin, or p120(cas)) with E-cadherin. However, EGF treatment of the MDA-MB-468 cell line dissociated actin, alpha-actinin, and vinculin from the E-cadherin-catenin complex, and this coincided with a robust phosphorylation of beta-catenin, plakoglobin/gamma-catenin, and p120(cas) on tyrosine residues. Furthermore, inactivation of the EGF receptor in serum-treated MDA-MB-468 cells with either a function-blocking antibody or EGF receptor kinase inhibitors mimicked the effects of serum starvation by stimulating both cellular aggregation and assembly of E-cadherin complexes with vinculin and actin. These results demonstrate that the EGF receptor directly regulates cell-cell adhesion through modulation of the interaction of E-cadherin with the actin cytoskeleton and thus substantiates the coordinate role of both of these molecules in tumor progression and metastasis.
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PMID:The epidermal growth factor receptor modulates the interaction of E-cadherin with the actin cytoskeleton. 953 96

Tyrosine phosphorylation of beta-catenin, an intracytoplasmic E-cadherin-binding protein, has been shown to disrupt the cadherin-mediated cell adhesion system in vitro. In order to investigate the relationships of expression and tyrosine phosphorylation of cadherin-catenin molecules and expression of growth factor receptor-tyrosine kinase with loose cell-to-cell adhesion, immunohistochemical staining for E-cadherin, alpha- and beta-catenin, phosphorylated tyrosine residues and tyrosine kinase receptors, including c-erbB-2, epidermal growth factor-receptor (EGF-R), c-met and K-sam, in 17 undifferentiated- and 10 differentiated-type human gastric cancers was performed. Loss or reduced expressions of E-cadherin and alpha- and beta-catenin (11, 11, 10 cancers, respectively) were observed in the former, but not the latter. Diffuse cytoplasmic staining of E-cadherin, alpha- and beta-catenin and phosphotyrosine residues was observed frequently in the undifferentiated-type cancers. The cytoplasmic localization of phosphotyrosine residues in undifferentiated-type cancers was correlated significantly with K-sam expression (P < 0.01) and diffuse cytoplasmic staining of E-cadherin (P < 0.05) and beta-catenin (P < 0.05). Expression of K-sam protein was detected significantly more frequently in undifferentiated- (6/17; P < 0.05) than differentiated-type adenocarcinomas whereas the converse applied to c-erbB-2 expression (8/10 of the latter, P < 0.05). Tyrosine phosphorylation of beta-catenin was directly confirmed in the protein extracts of one undifferentiated-type gastric cancer. These data indicate that alteration of tyrosine phosphorylation status associated with K-sam expression may cause the cytoplasmic distribution of cadherin-catenin molecules and loose cell-cell adhesion in undifferentiated-type gastric cancers.
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PMID:Expression of cadherin-catenin cell adhesion molecules, phosphorylated tyrosine residues and growth factor receptor-tyrosine kinases in gastric cancers. 976 19

We have sequenced and defined the expression during rat embryogenesis of the protocadherin fat, the murine homologue of a Drosophila tumour suppressor gene. As previously described for human fat, the sequence encodes a large protocadherin with 34 cadherin repeats, five epidermal growth factor (EGF)-like repeats containing a single laminin A-G domain and a putative transmembrane portion followed by a cytoplasmic sequence. This cytoplasmic sequence shows homology to the b-catenin binding regions of classical cadherin cytoplasmic tails and also ends with a PDZ domain-binding motif. In situ hybridization studies at E15 show that fat is predominately expressed in fetal epithelial cell layers and in the CNS, although expression is also seen in tongue musculature and condensing cartilage. Within the CNS, expression is seen in the germinal regions and in areas of developing cortex, and this neural expression pattern is also seen at later embryonic (E18) and postnatal stages. No labelling was seen in adult tissues except in the CNS, where the remnant of the germinal zones, as well as the dentate gyrus, continue to express fat.
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PMID:Expression of the rat homologue of the Drosophila fat tumour suppressor gene. 1007 90

The incidence of adenocarcinoma of the esophagus has been increasing in developing countries over the last three decades and probably reflects a genuine increase in the incidence of its recognized precursor lesion, Barrett's metaplasia. Despite advances in multimodality therapy, the prognosis for invasive esophageal adenocarcinoma is poor. An improved understanding of the molecular biology of this disease may allow improved diagnosis, therapy, and prognosis. We focus on recent developments in the molecular and cell biology of Barrett's metaplasia, a heterogeneous lesion affecting the transitional zone of the gastro-esophageal junction whose associated molecular alterations may vary both in nature and temporally. Early premalignant clones produce biological and genetic heterogeneity as seen by multiple p53 mutations, p16 mutations, aneuploidy, and abnormal methylation resulting in stepwise changes in differentiation, proliferation, and apoptosis, allowing disease progression under selective pressure. Abnormalities in expression of growth factors of the epidermal growth factor family and cell adhesion molecules, especially cadherin/catenin complexes, may occur early in invasion. Exploitation of these molecular events may lead to a more appropriate diagnosis and understanding of these lesions in the future.
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PMID:Molecular evolution of the metaplasia-dysplasia-adenocarcinoma sequence in the esophagus. 1023 32

p120-catenin (p120(ctn)) interacts with the cytoplasmic tail of cadherins and is thought to regulate cadherin clustering during formation of adherens junctions. Several observations suggest that p120 can both positively and negatively regulate cadherin adhesiveness depending on signals that so far remain unidentified. Although p120 tyrosine phosphorylation is a leading candidate, the role of this modification in normal and Src-transformed cells remains unknown. Here, as a first step toward pinpointing this role, we have employed two-dimensional tryptic mapping to directly identify the major sites of Src-induced p120 phosphorylation. Eight sites were identified by direct mutation of candidate tyrosines to phenylalanine and elimination of the accompanying spots on the two-dimensional maps. Identical sites were observed in vitro and in vivo, strongly suggesting that the physiologically important sites have been correctly identified. Changing all of these sites to phenylalanine resulted in a p120 mutant, p120-8F, that could not be efficiently phosphorylated by Src and failed to interact with SHP-1, a tyrosine phosphatase shown previously to interact selectively with tyrosine-phosphorylated p120 in cells stimulated with epidermal growth factor. Using selected tyrosine to phenylalanine p120 mutants as dominant negative reagents, it may now be possible to selectively block events postulated to be dependent on p120 tyrosine phosphorylation.
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PMID:Identification of Src phosphorylation sites in the catenin p120ctn. 1138 64

We previously demonstrated that a ligand-blocking monoclonal antibody (mAb) against the epidermal growth factor-receptor (EGF-R), LA1, induced morphological conversion from epithelial-like to epithelial of the human lung cancer cell line, H322. This was accompanied by an up-regulation of epithelial cadherin (E-cadherin) expression (Clin. Cancer Res. 5 (1999) 681). In the present paper, we show that mAb LA1 induces the epithelial-like to epithelial conversion of the human lung cancer cell line, A549. In A549 and H322 cells, which express a detectable amount of EGF-R (ErbB-1), ErbB-2, ErbB-3, and ErbB-4 receptors, the LA1 mAb induces up-regulation of the E-cadherin/catenin complex (alpha-, beta-, and gamma-catenins). This is associated with re-localization of E-cadherin, alpha-catenin, (and to a lesser extent beta-catenin), but not gamma-catenin. Additionally, we report that mAb LA1 inhibits cell motility. In contrast, epidermal growth factor (EGF) or heparin-binding EGF-like growth factor (HB-EGF) induces the epithelial-like to fibroblastoid conversion of A549 and H322 cell lines, slightly reduces the expression of E-cadherin and beta-catenin, but not alpha- and gamma-catenins, and stimulates cell motility. These studies demonstrate that EGF-R modulation regulates the E-cadherin/catenin complex and cell motility in human lung epithelial carcinoma cells. Our results may have important therapeutic implications for the treatment of invasive human lung carcinomas via the restoration of the cadherin/catenin complex using inhibitors of EGF-R.
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PMID:Regulation of E-cadherin/catenin complex patterns by epidermal growth factor receptor modulation in human lung cancer cells. 1205 67

Loss of E-cadherin-mediated cell-cell junctions has been correlated with cancer cell invasion and poor patient survival. p120-catenin has emerged as a key player in promoting E-cadherin stability and adherens junction integrity and has been proposed as a potential invasion suppressor by preventing release of cells from the constraints imposed by cadherin-mediated cell-cell adhesion. However, it has been proposed that tyrosine phosphorylation of p120 may contribute to cadherin-dependent junction disassembly during invasion. Here, we use small interfering RNA (siRNA) in A431 cells to show that knockdown of p120 promotes two-dimensional migration of cells. In contrast, p120 knockdown impairs epidermal growth factor-induced A431 invasion into three-dimensional matrix gels or in organotypic culture, whereas re-expression of siRNA-resistant p120, or a p120 isoform that cannot be phosphorylated on tyrosine, restores the collective mode of invasion employed by A431 cells in vitro. Thus, p120 promotes A431 cell invasion in a phosphorylation-independent manner. We show that the collective invasion of A431 cells depends on the presence of cadherin-mediated (P- and E-cadherin) cell-cell contacts, which are lost in cells where p120 expression is knocked down. Furthermore, membranous p120 is maintained in invasive squamous cell carcinomas in tumours suggesting that p120 may be important for the collective invasion of tumours cells in vivo.
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PMID:p120-catenin is required for the collective invasion of squamous cell carcinoma cells via a phosphorylation-independent mechanism. 1733 96


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