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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

Association of the c-erbB-2 oncogene product with the cadherin-catenin complex has been demonstrated in human cancer cell lines. Although beta-catenin and plakoglobin have been proven to be crucial for the association, no previous study has shown whether the interactions are direct or indirect. In the present study, the c-erbB-2 gene product was shown by far-Western blotting analysis to associate directly with both beta-catenin and plakoglobin through its cytoplasmic domain core region, which showed extensive homology with epidermal growth factor receptor. These data suggest that c-erbB-2-induced signaling is also directly liked to the cadherin-mediated cell adhesion and "invasion-suppressor" system through beta-catenin and plakoglobin in cancers.
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PMID:c-erbB-2 gene product directly associates with beta-catenin and plakoglobin. 770 5

The human papillomavirus type 16 (HPV-16), the type most often associated with cervical cancer, immortalizes primary keratinocytes and inhibits serum/calcium-stimulated differentiation in culture. In this study, we have used a model of keratinocyte immortalization based upon HPV-16 to analyze perturbation of function and expression of E-cadherin, a Ca(2+)-dependent cell-cell adhesion molecule expressed by normal keratinocytes, and its associated proteins. An immortalized keratinocyte cell line generated by cotransfection with HPV-16 E6 and E7 showed decreased membrane E-cadherin expression and redistribution of alpha-, beta-, and gamma-catenin from the undercoat membrane to the cytoplasm. No changes in the level of expression were seen. Selection of the immortalized keratinocyte cell line for resistance to differentiation generated a more transformed cell line with an invasive phenotype, down-regulated E-cadherin and alpha-catenin, and up-regulated the epidermal growth factor receptor (EGFr). Transfection of an E-cadherin expression construct into the differentiation-resistant cell line restored membrane-bound E-cadherin and catenin expression, down-regulated the EGFr, and reversed the invasive phenotype. These results indicate that overexpression of the EGFr correlates with perturbation of the E-cadherin/catenin complex seen in the HPV-16 E6- and E7-transfected keratinocytes and may underlie a functional interaction between growth-regulatory factors and adhesion molecules (E-cadherin/catenin).
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PMID:E-cadherin transfection down-regulates the epidermal growth factor receptor and reverses the invasive phenotype of human papilloma virus-transfected keratinocytes. 891 70

Intestinal trefoil factor (TFF3) is a member of the trefoil family of peptides, which are constitutively expressed in the gastrointestinal tract. TFF3 has been shown to promote migration of intestinal epithelial cells in vitro and to enhance epithelial restitution in vivo. In the present study, we show that the stimulatory effect of TFF3 on the migration of HT29 colonic carcinoma cells requires the perturbation of E-cadherin function, a calcium-dependent cell-cell adhesion molecule in epithelia. A rapid (< 1 minute) and specific tyrosine phosphorylation of beta-catenin and epidermal growth factor receptor was detected in cells treated with recombinant rat TFF3. No phosphorylation of E-cadherin or alpha-catenin was detected. Tyrosine phosphorylation of beta-catenin was associated with reduced membranous E-cadherin expression, perturbation of intercellular adhesion, and promotion of cell motility. These results suggest that TFF3 enhances cell migration through modulation of E-cadherin/catenin complex function. Tyrosine phosphorylation of beta-catenin and epidermal growth factor receptor seems to be involved in this process.
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PMID:Phosphorylation of beta-catenin and epidermal growth factor receptor by intestinal trefoil factor. 942 92

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

The E-cadherin-mediated cell adhesion system is now considered to be an "invasion suppressor system" in cancer cells. Dysfunction of the E-cadherin system due to mutations of the genes of E-cadherin and catenins has not been reported in colorectal cancer. Histologically, well-differentiated colorectal cancer cells are found to be scattered at the invasive front in primary lesions and form glands again in metastatic sites. We have reported the association and presence of signal transduction between c-erbB-2/epidermal growth factor receptor (EGF-R) and beta-catenin in human cancer cells. This temporal dysfunction of the E-cadherin system observed in colon cancers may be caused by tyrosine phosphorylation of beta-catenin through activated receptor-type tyrosine kinases. Overexpression of EGF-R and tyrosine phosphorylation of beta-catenin are often observed in "focal dedifferentiated cells" at the invasive front of colorectal cancers. In addition, beta-catenin expression is regulated by the APC tumor suppressor gene product. Thus the E-cadherin-catenin system may play important roles not only in invasion and metastasis but also in the carcinogenesis of colorectal cancer.
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PMID:[Dysfunction of E-cadherin-catenin system in invasion and metastasis of colorectal cancer]. 974 18

In the past decade, there have been major advances in the understanding of some of the mechanisms underlying tumour differentiation, invasion, and metastasis, in which cell-cell and cell-matrix adhesion molecules play a critical role. Cadherin/catenin complex and the integrins are the prime mediators of cell adhesion in normal and transformed cells, cadherin/catenin being largely responsible for intercellular adhesion and integrins for cell-extracellular matrix interactions. Intercellular and cell-matrix adhesion mediated by cadherin/catenin and integrins is likely to play a role in the control of both structural morphology and functional differentiation; hence, any loss of this control mechanism may well facilitate the neoplastic process. Indeed, in cancer cells, there is a co-ordinated down-regulation of both integrins and cadherins which correlates with tumour dedifferentiation. However, the expression and cellular localization of catenins do not always correlate with cadherin expression, since the catenins are rather promiscuous molecules which interact not only with E-cadherin, but also with growth regulatory and signalling molecules such as epidermal growth factor receptor and the adenomatous polyposis coli gene product.
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PMID:Integrins, cadherins, and catenins: molecular cross-talk in cancer cells. 987 32

The E-cadherin/catenin complex is a calcium-dependent cell-cell adhesion molecule, whose function is critical to the integrity of the adherens junction and which plays a role in the establishment and maintenance of normal epithelial morphology and differentiation. Loss of E-cadherin-mediated adhesion appears to be a fundamental aspect of the neoplastic phenotype which in some cases appears to be mediated by post-translational modifications (i.e. tyrosine phosphorylation) of its interacting proteins, the catenins which link E-cadherin to the actin cytoskeleton. There is increasing experimental evidence to suggest that epidermal growth factor receptor tyrosine phosphorylation may lead to the inactivation of the E-cadherin/catenin complex in cancer cells through its interaction with beta- or gamma-catenin in the cytoskeleton. Modulation of epidermal growth factor receptor activity by pharmacological agents has the potential to regulate a variety of cellular processes including adhesion, differentiation, and proliferation.
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PMID:The E-cadherin/epidermal growth factor receptor interaction: a hypothesis of reciprocal and reversible control of intercellular adhesion and cell proliferation. 1036 89

E-cadherin was originally viewed exclusively as a structural protein mediating cell-cell adhesion. More recently, its signaling functions have been recognized. Loss or downregulation of E-cadherin releases proteins, such as b-catenin and p120 catenin, from a membrane-bound state into the cytoplasm, which are known to regulate transcriptional activity. E-cadherin is known to interact with receptor tyrosine kinases, such as epidermal growth factor receptor (EGFR). However, previously, only the regulation of E-cadherin mediated adhesion through EGFR has been described and activation of EGFR was implicated in loss of cell adhesion, and increased cell migration and invasion. Now, Qian et al. (EMBO J 2004, 23:1739-48) describe that E-cadherin mediated adhesion inhibits receptor tyrosine kinase (RTK) activity. E-cadherin was found to interact through its extracellular domain with EGFR and other receptor tyrosine kinases, thereby decreasing receptor mobility and ligand-affinity. This is a novel mechanism by which E-cadherin inhibits RTKs, and suggests that downregulation of E-cadherin may contribute to the frequently observed activation of RTKs in tumors.
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PMID:No one-way street: cross-talk between e-cadherin and receptor tyrosine kinase (RTK) signaling: a mechanism to regulate RTK activity. 1566 13

Signaling pathways regulating the differentiation program of epidermal cells overlap widely with those activated during apoptosis. How differentiating cells remain protected from premature death, however, is still poorly defined. We show here that the phosphoinositide 3-kinase (PI3K)/Akt pathway is activated at early stages of mouse keratinocyte differentiation both in culture and in the intact epidermis in vivo. Expression of active Akt in keratinocytes promotes growth arrest and differentiation, whereas pharmacological blockade of PI3K inhibits the expression of "late" differentiation markers and leads to death of cells that would otherwise differentiate. Mechanistically, the activation of the PI3K/Akt pathway in keratinocyte differentiation depends on the activity of the epidermal growth factor receptor and Src families of tyrosine kinases and the engagement of E-cadherin-mediated adhesion. During this process, PI3K associates increasingly with cadherin-catenin protein complexes bearing tyrosine phosphorylated YXXM motifs. Thus, the PI3K signaling pathway regulates the choice between epidermal cell differentiation and death at the cross-talk between tyrosine kinases and cadherin-associated catenins.
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PMID:Phosphoinositide 3-kinase signaling to Akt promotes keratinocyte differentiation versus death. 1603 19


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