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PMID: 21383016 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

AMP-activated protein kinase (AMPK) activation and glycogen synthase kinase-3β (GSK-3β) inhibition induce Ca2+-independent deposition of tight junction components at the plasma membrane.

The Journal of biological chemistry ·Vol. 286 ·No. 19 ·2011-05-13 ·Pages 16879-90

Zhang L, Jouret F, Rinehart J, Sfakianos J, Mellman I, Lifton RP, Young LH, Caplan MJ

Abstract

Extracellular Ca(2+) is essential for the development of stable epithelial tight junctions. We find that in the absence of extracellular Ca(2+), AMP-activated protein kinase (AMPK) activation and glycogen synthase kinase (GSK)-3β inhibition independently induce the localization of epithelial tight junction components to the plasma membrane. The Ca(2+)-independent deposition of junctional proteins induced by AMPK activation and GSK-3β inhibition is independent of E-cadherin. Furthermore, the nectin-afadin system is required for the deposition of tight junction components induced by AMPK activation, but it is not required for that induced by GSK-3β inhibition. Phosphorylation studies demonstrate that afadin is a substrate for AMPK. These data demonstrate that two kinases involved in regulating cell growth and metabolism act through distinct pathways to influence the deposition of the components of epithelial tight junctions.

MeSH Terms
AMP-Activated Protein Kinases/metabolism,physiology Animals Cadherins/metabolism Calcium/metabolism Cell Adhesion Cell Membrane/metabolism Dogs Epithelium/metabolism Gene Expression Regulation, Enzymologic Glycogen Synthase Kinase 3/antagonists & inhibitors,physiology Glycogen Synthase Kinase 3 beta Membrane Proteins/antagonists & inhibitors,metabolism,physiology Microscopy, Fluorescence/methods Phosphoproteins/metabolism Phosphorylation RNA Interference Tight Junctions/metabolism Zonula Occludens-1 Protein
Chemicals
Cadherins Membrane Proteins Phosphoproteins Zonula Occludens-1 Protein Glycogen Synthase Kinase 3 beta Glycogen Synthase Kinase 3 AMP-Activated Protein Kinases Calcium
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Zhang Li
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Jouret Francois
Rinehart Jesse
Sfakianos Jeff
Mellman Ira
Lifton Richard P
Young Lawrence H
Caplan Michael J
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
1083-351X
DOI
10.1074/jbc.M110.186932
Published
2011-05-13
Epub
2011-00-07
Pages
16879-90
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC3089531
Subset
IM
Grants
NIDDK NIH HHS · P01 DK017433 · United States
NIDDK NIH HHS · R01 DK072614 · United States
PHS HHS · 072614 · United States
NIDDK NIH HHS · DK17433 · United States
External Links
PubMed source DOI: 10.1074/jbc.M110.186932 PMC Full Text View journal details
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