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PMID:18287330

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Citation

Guo, M, Breslin, JW, Wu, MH, Gottardi, CJ and Yuan, SY (2008) VE-cadherin and beta-catenin binding dynamics during histamine-induced endothelial hyperpermeability. Am. J. Physiol., Cell Physiol. 294:C977-84

Abstract

Beta-catenin plays an important role in the regulation of vascular endothelial cell-cell adhesions and barrier function by linking the VE-cadherin junction complex to the cytoskeleton. The purpose of this study was to evaluate the effect of beta-catenin and VE-cadherin interactions on endothelial permeability during inflammatory stimulation by histamine. We first assessed the ability of a beta-catenin binding polypeptide known as inhibitor of beta-catenin and T cell factor (ICAT) to compete beta-catenin binding to VE-cadherin in vitro. We then overexpressed recombinant FLAG-ICAT in human umbilical vein endothelial cells (HUVECs) to study its impact on endothelial barrier function controlled by cell-cell adhesions. The binding of beta-catenin to VE-cadherin was quantified before and after stimulation with histamine along with measurements of transendothelial electrical resistance (TER) and apparent permeability to albumin (P(a)) under the same conditions. The results showed that ICAT bound to beta-catenin and competitively inhibited binding of the VE-cadherin cytoplasmic domain to beta-catenin in a concentration-dependent manner. Overexpression of FLAG-ICAT in endothelial cell monolayers did not affect their basal permeability properties, as indicated by unaltered TER and P(a); however, the magnitude and duration of histamine-induced decreases in TER were significantly augmented. Likewise, the increase in P(a) in the presence of histamine was exacerbated. Overexpression of FLAG-ICAT also significantly decreased the level of beta-catenin-associated VE-cadherin following histamine stimulation. Taken together, these data suggest that inflammatory agents like histamine cause a transient and reversible disruption of binding between beta-catenin and VE-cadherin, during which endothelial permeability is elevated.

Links

PubMed Online version:10.1152/ajpcell.90607.2007

Keywords

Albumins/pharmacokinetics; Antigens, CD/metabolism; Cadherins/metabolism; Cell Cycle Proteins/genetics; Cell Cycle Proteins/metabolism; Cells, Cultured; Endothelial Cells; Endothelium, Vascular/drug effects; Endothelium, Vascular/physiology; Gene Expression Regulation; Histamine/pharmacology; Humans; Intercellular Junctions/drug effects; Intercellular Junctions/physiology; Intracellular Signaling Peptides and Proteins/genetics; Intracellular Signaling Peptides and Proteins/metabolism; Permeability/drug effects; Protein Binding; Transcription Factors/genetics; Transcription Factors/metabolism; beta Catenin/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:CADH5

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P35222

F

Seeded From UniProt

complete

HUMAN:CTNB1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P33151

F

Seeded From UniProt

complete

HUMAN:CTNB1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9NSA3

F

Seeded From UniProt

complete

HUMAN:CTNB1

enables

GO:0045296: cadherin binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P33151

F

Seeded From UniProt

complete

HUMAN:CNBP1

involved_in

GO:0032091: negative regulation of protein binding

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CNBP1

enables

GO:0008013: beta-catenin binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P35222

F

Seeded From UniProt

complete

HUMAN:CNBP1

part_of

GO:0005829: cytosol

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CNBP1

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:CNBP1

involved_in

GO:0002528: regulation of vascular permeability involved in acute inflammatory response

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CADH5

enables

GO:0008013: beta-catenin binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P35222

F

Seeded From UniProt

complete


See also

References

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