| PKC eta regulates occludin phosphorylation and epithelial tight junction integrity. | |
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MedLine Citation:
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PMID: 19114660 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PKC eta is expressed predominantly in the epithelial tissues; however, its role in the regulation of epithelial tight junctions (TJs) is unknown. We present evidence that PKC eta phosphorylates occludin on threonine residues (T403 and T404) and plays a crucial role in the assembly and/or maintenance of TJs in Caco-2 and MDCK cell monolayers. Inhibition of PKC eta by specific pseudo substrate inhibitor or knockdown of PKC eta by specific shRNA disrupts the junctional distribution of occludin and ZO-1 and compromises the epithelial barrier function. Expression of dominant negative, PKC eta(K394R) disrupts the TJ and barrier function, whereas wild-type PKC eta and constitutively active PKC eta(A161E) enhance the TJ integrity. Inhibition and knockdown of PKC eta or expression of PKC eta(K394R) induce dephosphorylation of occludin on threonine residues, whereas active PKC eta elevates occludin phosphorylation. PKC eta directly interacts with the C-terminal domain of occludin and phosphorylates it on highly conserved T403 and T404. T403/404A mutations result in the loss of occludin's ability to localize at the TJs, whereas T403/404D mutations attenuates the PKC eta inhibitor-mediated redistribution of occludin from the intercellular junctions. These results reveal an important mechanism of epithelial TJ regulation by PKC eta. |
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Authors:
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Takuya Suzuki; Bertha C Elias; Ankur Seth; Le Shen; Jerrold R Turner; Francesco Giorgianni; Dominic Desiderio; Ramareddy Guntaka; Radhakrishna Rao |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-12-29 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 106 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2009 Jan |
Date Detail:
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Created Date: 2009-01-07 Completed Date: 2009-02-13 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 61-6 Citation Subset: IM |
Affiliation:
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Department of Physiology, University of Tennessee Health Science Center, 894 Union Avenue, Memphis, TN 38163, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Binding Sites Cell Line Dogs Epithelium / metabolism, ultrastructure* Humans Membrane Proteins / genetics, metabolism* Mutation Phosphorylation Protein Kinase C / metabolism*, physiology Tight Junctions / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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1S10-RR16679/RR/NCRR NIH HHS; DK061931/DK/NIDDK NIH HHS; R01-AA12307/AA/NIAAA NIH HHS; R01-DK55532/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Membrane Proteins; 0/occludin; EC 2.7.1.-/protein kinase C eta; EC 2.7.11.13/Protein Kinase C |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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