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PMID: 12000714 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Interaction between the transforming growth factor-beta type II receptor/Smad pathway and beta-catenin during transforming growth factor-beta1-mediated adherens junction disassembly.

The American journal of pathology ·Vol. 160 ·No. 5 ·2002-05-00 ·Pages 1619-28

Tian YC, Phillips AO

Abstract

The aim of the current study was to examine the influence of transforming growth factor (TGF)-beta 1 on proximal tubular epithelial cell-cell interaction, with particular emphasis on the regulation of adherens junction complex formation. Stimulation of the proximal tubular cell line HK-2 cells by TGF-beta 1 led to loss of cell-cell contact and disassembly of both adherens and tight junctional complexes. Adherens junction disassembly was associated with reduction of both Triton-soluble and Triton-insoluble E-cadherin, and an increase in detergent-soluble beta-catenin. Under these conditions, immunoprecipitation and Western analysis demonstrated decreased association of beta-catenin, both with E-cadherin, alpha-catenin, and the cell cytoskeleton. Confocal microscopy after immunostaining, showed decreased intensity of peripheral E-cadherin staining, and redistribution of beta-catenin expression to a perinuclear location. Tight junction disassembly was manifest by a reduction in the expression of Triton-soluble occludin and ZO-1 by Western analysis and their disassociation manifested by immunostaining and confocal microscopy. Loss of cell-cell contact and disassembly of adherens junctions were seen after addition of TGF-beta 1 to the basolateral aspect of the cells. Immunoprecipitation experiments demonstrated co-localization of E-cadherin, beta-catenin, and TGF-beta 1 RII in unstimulated cells. After TGF-beta 1 stimulation, the TGF-beta 1 RII no longer associated with either E-cadherin or beta-catenin. Dissociation of the adherens junction protein from the TGF-beta 1 receptor was associated with increased beta-catenin tyrosine phosphorylation and decreased threonine phosphorylation. Furthermore after receptor ligand binding, beta-catenin became associated with the TGF-beta 1-signaling molecules Smad3 and Smad4.

MeSH Terms
Adherens Junctions/drug effects,metabolism Cell Line, Transformed Cell Polarity Cell Size/drug effects Cytoskeletal Proteins/metabolism DNA-Binding Proteins/metabolism Humans Immunohistochemistry Phosphorylation/drug effects Protein Binding/drug effects Protein Serine-Threonine Kinases Receptor, Transforming Growth Factor-beta Type II Receptors, Transforming Growth Factor beta/metabolism Signal Transduction/drug effects Smad3 Protein Smad4 Protein Tight Junctions/drug effects,metabolism Trans-Activators/metabolism Transforming Growth Factor beta/pharmacology Transforming Growth Factor beta1 beta Catenin
Chemicals
CTNNB1 protein, human Cytoskeletal Proteins DNA-Binding Proteins Receptors, Transforming Growth Factor beta SMAD3 protein, human SMAD4 protein, human Smad3 Protein Smad4 Protein TGFB1 protein, human Trans-Activators Transforming Growth Factor beta Transforming Growth Factor beta1 beta Catenin Protein Serine-Threonine Kinases Receptor, Transforming Growth Factor-beta Type II
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Tian Ya Chung
Institute of Nephrology, University of Wales College of Medicine, Heath Park, Cardiff, Wales.
Phillips Aled Owain
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/s0002-9440(10)61109-1
Published
2002-05-00
Pages
1619-28
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1850871
Subset
IM
Grants
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1016/s0002-9440(10)61109-1 PMC Full Text View journal details
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