The Experts below are selected from a list of 127707 Experts worldwide ranked by ideXlab platform
Rolf Kemler - One of the best experts on this subject based on the ideXlab platform.
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Protein kinase CKII regulates the interaction of beta-Catenin with alpha-Catenin and its protein stability
Journal of Cell Science, 2002Co-Authors: Rolf KemlerAbstract:β-Catenin is a multi-functional cellular component and a substrate for several protein kinases. Here we investigated the interaction of protein kinase CKII (casein kinase II) and β-Catenin. We show that CKII phosphorylates the N-terminal region of β-Catenin and we identified Ser29, Thr102, and Thr112 as substrates for the enzyme. We provide evidence that CKII regulates the cytoplasmic stability of β-Catenin and acts synergistically with GSK-3β in the multi-protein complex that controls the degradation of β-Catenin. In comparing wild-type and Ser/Thr-mutantβ -Catenin, a decreased affinity of the mutant protein to α-Catenin was observed. Moreover, kinase assays in vitro demonstrate a CKII-dependent increase in the binding of wild-type β-Catenin with α-Catenin. In line with that, cells expressing Ser/Thr-mutant β-Catenin exhibit an increased migratory potential, which correlates with an enhanced cytosolic localization and a reduced association with the cytoskeleton of the mutant protein. From these results we conclude that CKII regulates the function ofβ -Catenin in the cadherin adhesion complex as well as its cytoplasmic stability.
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Cadherins and Catenins in development
Current Opinion in Cell Biology, 1996Co-Authors: Otmar Huber, Christiane Bierkamp, Rolf KemlerAbstract:Abstract Cadherins and Catenins represent key molecules during development. Recent findings demonstrate the involvement of cadherins and Catenins in signaling pathways. In a working hypothesis, signaling via β-Catenin regulates the epithelial—mesenchymal transition in vertebrate development.
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cadherin Catenin complex protein interactions and their implications for cadherin function
Journal of Cellular Biochemistry, 1996Co-Authors: Hermann Aberle, Hillel Schwartz, Rolf KemlerAbstract: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 β-Catenin or plakoglobin (γ-Catenin). β-Catenin and plakoglobin bind directly to α-Catenin, giving rise to two distinct cadherin-Catenin complexes (CCC). α-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 β-Catenin. © 1996 Wiley-Liss, Inc.
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beta Catenin mediates the interaction of the cadherin Catenin complex with epidermal growth factor receptor
Journal of Cell Biology, 1994Co-Authors: Heinz Hoschuetzky, Hermann Aberle, Rolf KemlerAbstract:Catenins mediate the linkage of classical cadherins with actin microfilaments and are part of a higher order protein structure by which cadherins are connected to other cytoplasmic and transmembrane proteins. The ratio of actin-bound to free cadherin-Catenin complex, which varies depending on the type and growth rate of cells, is thought to be altered by cellular signals, such as those associated with mitosis, polarization of cells and growth factors during development. EGF induces an immediate tyrosine phosphorylation of beta-Catenin and gamma-Catenin (plakoglobin). We show here an association of the EGF-receptor with the cadherin-Catenin complex. Using recombinant proteins we demonstrate the interaction of EGF-receptor and beta-Catenin in in vitro kinase assays. This interaction is mediated by the evolutionarily conserved central "core" region of beta-Catenin. These results suggest that Catenins represent an important link between EGF-induced signal transduction and cadherin function.
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from cadherins to Catenins cytoplasmic protein interactions and regulation of cell adhesion
Trends in Genetics, 1993Co-Authors: Rolf KemlerAbstract:Abstract Classical cadherins are complexed via their cytoplasmic domains with α-, β- and γ-Catenin. This complex formation links cadherins to the actin filament network and to other transmembrane and cytoplasmic proteins. α-Catenin is homologous to vinculin, and β-Catenin to the product of the Drosophila gene armadillo, while γ-Catenin seems to be identical to plakoglobin. Catenins are part of a higher order protein structure that is of crucial importance for the adhesive function of cadherins. A working model of the construction and regulation of this multiprotein interaction is proposed.
Naoki Mochizuki - One of the best experts on this subject based on the ideXlab platform.
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vascular endothelial cadherin stabilizes at cell cell junctions by anchoring to circumferential actin bundles through α and β Catenins in cyclic amp epac rap1 signal activated endothelial cells
Molecular Biology of the Cell, 2010Co-Authors: Kazuomi Noda, Jianghui Zhang, Shigetomo Fukuhara, Satoshi Kunimoto, Michihiro Yoshimura, Naoki MochizukiAbstract:Vascular endothelial (VE)-cadherin is a cell–cell adhesion molecule involved in endothelial barrier functions. Previously, we reported that cAMP-Epac-Rap1 signal enhances VE-cadherin–dependent cell adhesion. Here, we further scrutinized how cAMP-Epac-Rap1 pathway promotes stabilization of VE-cadherin at the cell–cell contacts. Forskolin induced circumferential actin bundling and accumulation of VE-cadherin fused with green fluorescence protein (VEC-GFP) on the bundled actin filaments. Fluorescence recovery after photobleaching (FRAP) analyses using VEC-GFP revealed that forskolin stabilizes VE-cadherin at cell–cell contacts. These effects of forskolin were mimicked by an activator for Epac but not by that for protein kinase A. Forskolin-induced both accumulation and stabilization of junctional VEC-GFP was impeded by latrunculin A. VE-cadherin, α-Catenin, and β-Catenin were dispensable for forskolin-induced circumferential actin bundling, indicating that homophilic VE-cadherin association is not the trigger of actin bundling. Requirement of α- and β-Catenins for forskolin-induced stabilization of VE-cadherin on the actin bundles was confirmed by FRAP analyses using VEC-GFP mutants, supporting the classical model that α-Catenin could potentially link the bundled actin to cadherin. Collectively, circumferential actin bundle formation and subsequent linkage between actin bundles and VE-cadherin through α- and β-Catenins are important for the stabilization of VE-cadherin at the cell–cell contacts in cAMP-Epac-Rap1 signal-activated cells.
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vascular endothelial cadherin stabilizes at cell cell junctions by anchoring to circumferential actin bundles through α and β Catenins in cyclic amp epac rap1 signal activated endothelial cells
Molecular Biology of the Cell, 2010Co-Authors: Kazuomi Noda, Jianghui Zhang, Shigetomo Fukuhara, Satoshi Kunimoto, Michihiro Yoshimura, Naoki MochizukiAbstract:: Vascular endothelial (VE)-cadherin is a cell-cell adhesion molecule involved in endothelial barrier functions. Previously, we reported that cAMP-Epac-Rap1 signal enhances VE-cadherin-dependent cell adhesion. Here, we further scrutinized how cAMP-Epac-Rap1 pathway promotes stabilization of VE-cadherin at the cell-cell contacts. Forskolin induced circumferential actin bundling and accumulation of VE-cadherin fused with green fluorescence protein (VEC-GFP) on the bundled actin filaments. Fluorescence recovery after photobleaching (FRAP) analyses using VEC-GFP revealed that forskolin stabilizes VE-cadherin at cell-cell contacts. These effects of forskolin were mimicked by an activator for Epac but not by that for protein kinase A. Forskolin-induced both accumulation and stabilization of junctional VEC-GFP was impeded by latrunculin A. VE-cadherin, alpha-Catenin, and beta-Catenin were dispensable for forskolin-induced circumferential actin bundling, indicating that homophilic VE-cadherin association is not the trigger of actin bundling. Requirement of alpha- and beta-Catenins for forskolin-induced stabilization of VE-cadherin on the actin bundles was confirmed by FRAP analyses using VEC-GFP mutants, supporting the classical model that alpha-Catenin could potentially link the bundled actin to cadherin. Collectively, circumferential actin bundle formation and subsequent linkage between actin bundles and VE-cadherin through alpha- and beta-Catenins are important for the stabilization of VE-cadherin at the cell-cell contacts in cAMP-Epac-Rap1 signal-activated cells.
Kazuomi Noda - One of the best experts on this subject based on the ideXlab platform.
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vascular endothelial cadherin stabilizes at cell cell junctions by anchoring to circumferential actin bundles through α and β Catenins in cyclic amp epac rap1 signal activated endothelial cells
Molecular Biology of the Cell, 2010Co-Authors: Kazuomi Noda, Jianghui Zhang, Shigetomo Fukuhara, Satoshi Kunimoto, Michihiro Yoshimura, Naoki MochizukiAbstract:Vascular endothelial (VE)-cadherin is a cell–cell adhesion molecule involved in endothelial barrier functions. Previously, we reported that cAMP-Epac-Rap1 signal enhances VE-cadherin–dependent cell adhesion. Here, we further scrutinized how cAMP-Epac-Rap1 pathway promotes stabilization of VE-cadherin at the cell–cell contacts. Forskolin induced circumferential actin bundling and accumulation of VE-cadherin fused with green fluorescence protein (VEC-GFP) on the bundled actin filaments. Fluorescence recovery after photobleaching (FRAP) analyses using VEC-GFP revealed that forskolin stabilizes VE-cadherin at cell–cell contacts. These effects of forskolin were mimicked by an activator for Epac but not by that for protein kinase A. Forskolin-induced both accumulation and stabilization of junctional VEC-GFP was impeded by latrunculin A. VE-cadherin, α-Catenin, and β-Catenin were dispensable for forskolin-induced circumferential actin bundling, indicating that homophilic VE-cadherin association is not the trigger of actin bundling. Requirement of α- and β-Catenins for forskolin-induced stabilization of VE-cadherin on the actin bundles was confirmed by FRAP analyses using VEC-GFP mutants, supporting the classical model that α-Catenin could potentially link the bundled actin to cadherin. Collectively, circumferential actin bundle formation and subsequent linkage between actin bundles and VE-cadherin through α- and β-Catenins are important for the stabilization of VE-cadherin at the cell–cell contacts in cAMP-Epac-Rap1 signal-activated cells.
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vascular endothelial cadherin stabilizes at cell cell junctions by anchoring to circumferential actin bundles through α and β Catenins in cyclic amp epac rap1 signal activated endothelial cells
Molecular Biology of the Cell, 2010Co-Authors: Kazuomi Noda, Jianghui Zhang, Shigetomo Fukuhara, Satoshi Kunimoto, Michihiro Yoshimura, Naoki MochizukiAbstract:: Vascular endothelial (VE)-cadherin is a cell-cell adhesion molecule involved in endothelial barrier functions. Previously, we reported that cAMP-Epac-Rap1 signal enhances VE-cadherin-dependent cell adhesion. Here, we further scrutinized how cAMP-Epac-Rap1 pathway promotes stabilization of VE-cadherin at the cell-cell contacts. Forskolin induced circumferential actin bundling and accumulation of VE-cadherin fused with green fluorescence protein (VEC-GFP) on the bundled actin filaments. Fluorescence recovery after photobleaching (FRAP) analyses using VEC-GFP revealed that forskolin stabilizes VE-cadherin at cell-cell contacts. These effects of forskolin were mimicked by an activator for Epac but not by that for protein kinase A. Forskolin-induced both accumulation and stabilization of junctional VEC-GFP was impeded by latrunculin A. VE-cadherin, alpha-Catenin, and beta-Catenin were dispensable for forskolin-induced circumferential actin bundling, indicating that homophilic VE-cadherin association is not the trigger of actin bundling. Requirement of alpha- and beta-Catenins for forskolin-induced stabilization of VE-cadherin on the actin bundles was confirmed by FRAP analyses using VEC-GFP mutants, supporting the classical model that alpha-Catenin could potentially link the bundled actin to cadherin. Collectively, circumferential actin bundle formation and subsequent linkage between actin bundles and VE-cadherin through alpha- and beta-Catenins are important for the stabilization of VE-cadherin at the cell-cell contacts in cAMP-Epac-Rap1 signal-activated cells.
Michihiro Yoshimura - One of the best experts on this subject based on the ideXlab platform.
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vascular endothelial cadherin stabilizes at cell cell junctions by anchoring to circumferential actin bundles through α and β Catenins in cyclic amp epac rap1 signal activated endothelial cells
Molecular Biology of the Cell, 2010Co-Authors: Kazuomi Noda, Jianghui Zhang, Shigetomo Fukuhara, Satoshi Kunimoto, Michihiro Yoshimura, Naoki MochizukiAbstract:Vascular endothelial (VE)-cadherin is a cell–cell adhesion molecule involved in endothelial barrier functions. Previously, we reported that cAMP-Epac-Rap1 signal enhances VE-cadherin–dependent cell adhesion. Here, we further scrutinized how cAMP-Epac-Rap1 pathway promotes stabilization of VE-cadherin at the cell–cell contacts. Forskolin induced circumferential actin bundling and accumulation of VE-cadherin fused with green fluorescence protein (VEC-GFP) on the bundled actin filaments. Fluorescence recovery after photobleaching (FRAP) analyses using VEC-GFP revealed that forskolin stabilizes VE-cadherin at cell–cell contacts. These effects of forskolin were mimicked by an activator for Epac but not by that for protein kinase A. Forskolin-induced both accumulation and stabilization of junctional VEC-GFP was impeded by latrunculin A. VE-cadherin, α-Catenin, and β-Catenin were dispensable for forskolin-induced circumferential actin bundling, indicating that homophilic VE-cadherin association is not the trigger of actin bundling. Requirement of α- and β-Catenins for forskolin-induced stabilization of VE-cadherin on the actin bundles was confirmed by FRAP analyses using VEC-GFP mutants, supporting the classical model that α-Catenin could potentially link the bundled actin to cadherin. Collectively, circumferential actin bundle formation and subsequent linkage between actin bundles and VE-cadherin through α- and β-Catenins are important for the stabilization of VE-cadherin at the cell–cell contacts in cAMP-Epac-Rap1 signal-activated cells.
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vascular endothelial cadherin stabilizes at cell cell junctions by anchoring to circumferential actin bundles through α and β Catenins in cyclic amp epac rap1 signal activated endothelial cells
Molecular Biology of the Cell, 2010Co-Authors: Kazuomi Noda, Jianghui Zhang, Shigetomo Fukuhara, Satoshi Kunimoto, Michihiro Yoshimura, Naoki MochizukiAbstract:: Vascular endothelial (VE)-cadherin is a cell-cell adhesion molecule involved in endothelial barrier functions. Previously, we reported that cAMP-Epac-Rap1 signal enhances VE-cadherin-dependent cell adhesion. Here, we further scrutinized how cAMP-Epac-Rap1 pathway promotes stabilization of VE-cadherin at the cell-cell contacts. Forskolin induced circumferential actin bundling and accumulation of VE-cadherin fused with green fluorescence protein (VEC-GFP) on the bundled actin filaments. Fluorescence recovery after photobleaching (FRAP) analyses using VEC-GFP revealed that forskolin stabilizes VE-cadherin at cell-cell contacts. These effects of forskolin were mimicked by an activator for Epac but not by that for protein kinase A. Forskolin-induced both accumulation and stabilization of junctional VEC-GFP was impeded by latrunculin A. VE-cadherin, alpha-Catenin, and beta-Catenin were dispensable for forskolin-induced circumferential actin bundling, indicating that homophilic VE-cadherin association is not the trigger of actin bundling. Requirement of alpha- and beta-Catenins for forskolin-induced stabilization of VE-cadherin on the actin bundles was confirmed by FRAP analyses using VEC-GFP mutants, supporting the classical model that alpha-Catenin could potentially link the bundled actin to cadherin. Collectively, circumferential actin bundle formation and subsequent linkage between actin bundles and VE-cadherin through alpha- and beta-Catenins are important for the stabilization of VE-cadherin at the cell-cell contacts in cAMP-Epac-Rap1 signal-activated cells.
Satoshi Kunimoto - One of the best experts on this subject based on the ideXlab platform.
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vascular endothelial cadherin stabilizes at cell cell junctions by anchoring to circumferential actin bundles through α and β Catenins in cyclic amp epac rap1 signal activated endothelial cells
Molecular Biology of the Cell, 2010Co-Authors: Kazuomi Noda, Jianghui Zhang, Shigetomo Fukuhara, Satoshi Kunimoto, Michihiro Yoshimura, Naoki MochizukiAbstract:Vascular endothelial (VE)-cadherin is a cell–cell adhesion molecule involved in endothelial barrier functions. Previously, we reported that cAMP-Epac-Rap1 signal enhances VE-cadherin–dependent cell adhesion. Here, we further scrutinized how cAMP-Epac-Rap1 pathway promotes stabilization of VE-cadherin at the cell–cell contacts. Forskolin induced circumferential actin bundling and accumulation of VE-cadherin fused with green fluorescence protein (VEC-GFP) on the bundled actin filaments. Fluorescence recovery after photobleaching (FRAP) analyses using VEC-GFP revealed that forskolin stabilizes VE-cadherin at cell–cell contacts. These effects of forskolin were mimicked by an activator for Epac but not by that for protein kinase A. Forskolin-induced both accumulation and stabilization of junctional VEC-GFP was impeded by latrunculin A. VE-cadherin, α-Catenin, and β-Catenin were dispensable for forskolin-induced circumferential actin bundling, indicating that homophilic VE-cadherin association is not the trigger of actin bundling. Requirement of α- and β-Catenins for forskolin-induced stabilization of VE-cadherin on the actin bundles was confirmed by FRAP analyses using VEC-GFP mutants, supporting the classical model that α-Catenin could potentially link the bundled actin to cadherin. Collectively, circumferential actin bundle formation and subsequent linkage between actin bundles and VE-cadherin through α- and β-Catenins are important for the stabilization of VE-cadherin at the cell–cell contacts in cAMP-Epac-Rap1 signal-activated cells.
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vascular endothelial cadherin stabilizes at cell cell junctions by anchoring to circumferential actin bundles through α and β Catenins in cyclic amp epac rap1 signal activated endothelial cells
Molecular Biology of the Cell, 2010Co-Authors: Kazuomi Noda, Jianghui Zhang, Shigetomo Fukuhara, Satoshi Kunimoto, Michihiro Yoshimura, Naoki MochizukiAbstract:: Vascular endothelial (VE)-cadherin is a cell-cell adhesion molecule involved in endothelial barrier functions. Previously, we reported that cAMP-Epac-Rap1 signal enhances VE-cadherin-dependent cell adhesion. Here, we further scrutinized how cAMP-Epac-Rap1 pathway promotes stabilization of VE-cadherin at the cell-cell contacts. Forskolin induced circumferential actin bundling and accumulation of VE-cadherin fused with green fluorescence protein (VEC-GFP) on the bundled actin filaments. Fluorescence recovery after photobleaching (FRAP) analyses using VEC-GFP revealed that forskolin stabilizes VE-cadherin at cell-cell contacts. These effects of forskolin were mimicked by an activator for Epac but not by that for protein kinase A. Forskolin-induced both accumulation and stabilization of junctional VEC-GFP was impeded by latrunculin A. VE-cadherin, alpha-Catenin, and beta-Catenin were dispensable for forskolin-induced circumferential actin bundling, indicating that homophilic VE-cadherin association is not the trigger of actin bundling. Requirement of alpha- and beta-Catenins for forskolin-induced stabilization of VE-cadherin on the actin bundles was confirmed by FRAP analyses using VEC-GFP mutants, supporting the classical model that alpha-Catenin could potentially link the bundled actin to cadherin. Collectively, circumferential actin bundle formation and subsequent linkage between actin bundles and VE-cadherin through alpha- and beta-Catenins are important for the stabilization of VE-cadherin at the cell-cell contacts in cAMP-Epac-Rap1 signal-activated cells.
