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)

Endothelial barrier function depends on the integrity of intercellular adherens junctions controlled by the association of VE-cadherin/catenin complex with cortical actin filaments. Both tyrosine phosphorylation/dephosphorylation of junctional proteins and actin reorganization mediated by rho-GTPases regulate barrier function but the relationship between these regulatory mechanisms is unclear. Here we studied the effects of factors increasing protein tyrosine phosphorylation, pervanadate (PV) and VEGF, on distribution of VE-cadherin, F-actin polymerization and transendothelial electrical resistance (TER) in human umbilical vein endothelial cells (HUVECs). Changes in protein tyrosine phosphorylation of cytoplasmic and junctional proteins, as well as the activity of rho-GTPase racl, were also measured. We report for the first time that PV and VEGF induced a rapid transient increase in endothelial barrier function accompanied by rac1 activation, a differentiated tyrosine phosphorylation of the VE-cadherin/catenin complex, recruitment of actin filament to cell junctions and ruffle formation. A sustained decrease in endothelial barrier function was observed at later times of PV and VEGF treatment. Expression of dominant negative rac1, N17rac1 abolished the barrier-enhancing effects of PV and VEGF, while the sustained decrease in barrier function was unaffected. These observations bring into focus early short-term effects of protein tyrosine phosphorylation in cells, often overshadowed by more pronounced and long-lasting later effects and may play an important role in the regulation of endothelial barrier function.
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PMID:Tyrosine phosphorylation and the small GTPase rac cross-talk in regulation of endothelial barrier function. 1626 81

The endothelial adherens junctions (AJs) consist of trans-oligomers of membrane spanning vascular endothelial (VE)-cadherin proteins, which bind beta-catenin through their cytoplasmic domain. beta-Catenin in turn binds alpha-catenin and connects the AJ complex with the actin cytoskeleton. We addressed the in vivo effects of loss of VE-cadherin interactions on lung vascular endothelial permeability and the role of specific Rho GTPase effectors in regulating the increase in permeability induced by AJ destabilization. We used cationic liposomes encapsulating the mutant of VE-cadherin lacking the extracellular domain (DeltaEXD) to interfere with AJ assembly in mouse lung endothelial cells. We observed that lung vascular permeability (quantified as microvessel filtration coefficient [K(f,c)]) was increased 5-fold in lungs expressing DeltaEXD. This did not occur to the same degree on expression of the VE-cadherin mutant, DeltaEXDDeltabeta, lacking the beta-catenin-binding site. The increased vascular permeability was the result of destabilization of VE-cadherin homotypic interaction induced by a shift in the binding of beta-catenin from wild-type VE-cadherin to the expressed DeltaEXD mutant. Because DeltaEXD expression in endothelial cells activated the Rho GTPase Cdc42, we addressed its role in the mechanism of increased endothelial permeability induced by AJ destabilization. Coexpression of dominant-negative Cdc42 (N17Cdc42) prevented the increase in K(f,c) induced by DeltaEXD. This was attributed to inhibition of the association of alpha-catenin with the DeltaEXD-beta-catenin complex. The results demonstrate that Cdc42 regulates AJ permeability by controlling the binding of alpha-catenin with beta-catenin and the consequent interaction of the VE-cadherin/catenin complex with the actin cytoskeleton.
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PMID:Cdc42 regulates adherens junction stability and endothelial permeability by inducing alpha-catenin interaction with the vascular endothelial cadherin complex. 1632 81

Matrilysin, MMP-7, is an important target for anti-metastasis therapy of colorectal cancer because it is a strong proteolytic factor secreted from the cancer cell itself and it induces tumor angiogenesis. In a previous report, we showed that matrilysin accelerated human umbilical vein endothelial cell (HUVEC) proliferation in low serum conditioned medium. In the present study, we show that matrilysin stimulation decreased VE-cadherin expression, induced accumulation of beta-catenin in the nucleus of the HUVEC, and up-regulated matrilysin mRNA expression. These results compel a hypothesis that matrilysin cleaves VE-cadherin and releases beta-catenin from the VE-cadherin/catenin complex; the free beta-catenin can activate T-cell factor (Tcf) DNA binding protein, which accelerates cell proliferation and matrilysin expression.
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PMID:Matrilysin (MMP-7) degrades VE-cadherin and accelerates accumulation of beta-catenin in the nucleus of human umbilical vein endothelial cells. 1639 47

Receptor protein tyrosine phosphatase rho (RPTPrho/PTPRT) is a transmembrane protein that is highly expressed in the developing and adult central nervous system. It is a member of the RPTP R2B subfamily, which includes PTPkappa, PTPmu and PCP-2. Glutathione-S-transferase (GST) pulldown assays were used to show that RPTPrho interacts with several adherens junctional proteins in brain, including E-cadherin, N-cadherin, VE-cadherin (cadherin-5), desmoglein, alpha, beta and gamma catenin, p120(ctn) and alpha-actinin. With the exception of E-cadherin and alpha-actinin, binding was considerably reduced at high sodium concentrations. Furthermore, immunoprecipitation phosphatase assays indicated that E-cadherin, and to a far lesser extent p120(ctn), were tyrosine dephosphorylated by a recombinant RPTPrho intracellular fragment, and thus, were likely to be primary substrates for RPTPrho. The interaction of RPTPrho with adherens junctional components suggests that this phosphatase may transduce extracellular signals to the actin cytoskeleton and thereby play a role in regulating cadherin-mediated cell adhesion in the central nervous system.
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PMID:Intracellular substrates of brain-enriched receptor protein tyrosine phosphatase rho (RPTPrho/PTPRT). 1697 35

In the present review article the role of cadherin/catenin complex in cases of malignant melanoma is discussed in some detail. Cadherins represent the most important superfamily of adhesion molecules with epithelial E-cadherin being the most studied. Its role in normal state as well as in cancer invasion and metastasis and some other pathologies is crucial. E-cadherin expression is altered in malignant melanomas and its downregulation or absence is associated with melanoma invasion and metastasis potential. A shift from E-cadherin expression to neural N-cadherin expression in melanocytes is also detected in malignant melanomas formation. In addition, a discussion regarding the role of placental P-cadherin and vascular endothelial VE-cadherin as well as the recently identified molecule of dysadherin, is attempted in brief.
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PMID:The role of cadherin/catenin complex in malignant melanoma. 1708 10

Mouse tibial growth plates were examined for the presence of adhesion molecules using immunohistochemistry and RT-PCR. All of the components of the classical cadherin/catenin complex (cadherin, alpha-, beta-, and gamma-catenin), as well as a heavy presence of p120, were identified in the murine growth plate. All of the major cadherins (1-5, 11, 13, and 15) were, for the first time, identified and localized in the murine growth plate. We have demonstrated that most of the cadherins and catenins reside in the zone of hypertrophy. Only alpha-catenin and E-, P-, R-, and VE-cadherin were found in all regions of the growth plate. The results for T-cadherin were inconclusive.
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PMID:Immunohistochemical localization of cadherin and catenin adhesion molecules in the murine growth plate. 1743 49

Marburg virus (MARV) infection often causes fulminant shock due to pathologic immune responses and alterations of the vascular system. Cytokines released from virus-infected monocytes/macrophages provoke endothelial activation and vascular hyperpermeability and contribute to the development of shock. Tyrosine phosphorylation of cell-junction proteins is important for the regulation of paraendothelial barrier function. We showed that mediators released from MARV-infected monocytes/macrophages, as well as recombinant tumor necrosis factor (TNF)- alpha /H2O2 and interferon (IFN)- gamma , caused tyrosine phosphorylation of platelet endothelial cell adhesion molecule-1 (PECAM-1) but not of the vascular endothelial (VE) cadherin/catenin complex proteins. Tyrosine phosphorylation of PECAM-1 was associated with delayed opening of interendothelial junctions. Interestingly, we observed an early increase in water permeability in response to TNF- alpha /H2O2 that was not due to an opening of the interendothelial junctions. These data indicate 2 distinct mechanisms for the TNF- alpha /H2O2-mediated decrease in endothelial barrier function involving tyrosine phosphorylation of PECAM-1 but not requiring tyrosine phosphorylation of VE-cadherin or catenin proteins.
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PMID:Breakdown of paraendothelial barrier function during Marburg virus infection is associated with early tyrosine phosphorylation of platelet endothelial cell adhesion molecule-1. 1794 Sep 69

In vascular endothelium, adherens junctions between endothelial cells are composed of VE-cadherin (vascular endothelial cadherin), an adhesive receptor that is crucial for the proper assembly of vascular structures and the maintenance of vascular integrity. As a classical cadherin, VE-cadherin links endothelial cells together by homophilic interactions mediated by its extracellular part and associates intracellularly with the actin cytoskeleton via catenins. Although, from structural crystallographic data, a dimeric structure arranged in a trans orientation has emerged as a potential mechanism of cell-cell adhesion, the cadherin organization within adherens junctions remains controversial. Concerning VE-cadherin, its extracellular part possesses the capacity to self-associate in solution as hexamers consisting of three antiparallel cadherin dimers. VE-cadherin-based adherens junctions were reconstituted in vitro by assembly of a VE-cadherin EC (extracellular repeat) 1-EC4 hexamer at the surfaces of liposomes. The artificial adherens junctions revealed by cryoelectron microscopy appear as a two-dimensional self-assembly of hexameric structures. This cadherin organization is reminiscent of that found in native desmosomal junctions. Further structural studies performed on native VE-cadherin junctions would provide a better understanding of the cadherin organization within adherens junctions. Homophilic interactions between cadherins are strengthened intracellularly by connection to the actin cytoskeleton. Recently, we have discovered that annexin 2, an actin-binding protein connects the VE-cadherin-catenin complex to the actin cytoskeleton. This novel link is labile and promotes the endothelial cell switch from a quiescent to an angiogenic state.
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PMID:Structure of artificial and natural VE-cadherin-based adherens junctions. 1836 60

The integrity of the endothelial monolayer is essential to blood vessel homeostasis and active regulation of endothelial permeability. The FGF system plays important roles in a wide variety of physiologic and pathologic conditions; however, its role in the adult vasculature has not been defined. To assess the role of the FGF system in the adult endothelial monolayer, we disrupted FGF signaling in bovine aortic endothelial cells and human saphenous vein endothelial cells in vitro and in adult mouse and rat endothelial cells in vivo using soluble FGF traps or a dominant inhibitor of all FGF receptors. The inhibition of FGF signaling using these approaches resulted in dissociation of the VE-cadherin/p120-catenin complex and disassembly of adherens and tight junctions, which progressed to loss of endothelial cells, severe impairment of the endothelial barrier function, and finally, disintegration of the vasculature. Thus, FGF signaling plays a key role in the maintenance of vascular integrity.
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PMID:The FGF system has a key role in regulating vascular integrity. 1877 42

Endothelial cells (ECs) express VE-cadherin and N-cadherin, and recent data suggest that VE-cadherin levels are dependent on N-cadherin expression. While investigating changes in N-cadherin levels during endothelial monolayer maturation, the authors found that VE-cadherin levels are maintained in ECs despite a decrease in N-cadherin, suggesting that VE-cadherin levels may not depend on N-cadherin. Knockdown of N-cadherin did not affect VE-cadherin levels in ECs with low endogenous N-cadherin expression. Surprisingly, however, knockdown of N-cadherin in ECs with high endogenous N-cadherin expression increased VE-cadherin levels, suggesting an inverse relationship between the two. This was further supported by a decrease in VE-cadherin following overexpression of N-cadherin. Experiments in which p120, a catenin that binds N- and VE-cadherin, was knocked down or overexpressed indicate that these two cadherins compete for p120. These data demonstrate that VE-cadherin levels are not directly related to N-cadherin levels but may be inversely related due to competition for p120.
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PMID:N-cadherin levels in endothelial cells are regulated by monolayer maturity and p120 availability. 1897 98


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