Linked Life Data

21545357

Source:http://linkedlifedata.com/resource/pubmed/id/21545357

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-6-29
pubmed:abstractText
Protein kinases play an important role in the regulation of epithelial tight junctions. In the present study, we investigated the role of PKC? (protein kinase C?) in tight junction regulation in Caco-2 and MDCK (Madin-Darby canine kidney) cell monolayers. Inhibition of PKC? by a specific PKC? pseudosubstrate peptide results in redistribution of occludin and ZO-1 (zona occludens 1) from the intercellular junctions and disruption of barrier function without affecting cell viability. Reduced expression of PKC? by antisense oligonucleotide or shRNA (short hairpin RNA) also results in compromised tight junction integrity. Inhibition or knockdown of PKC? delays calcium-induced assembly of tight junctions. Tight junction disruption by PKC? pseudosubstrate is associated with the dephosphorylation of occludin and ZO-1 on serine and threonine residues. PKC? directly binds to the C-terminal domain of occludin and phosphorylates it on threonine residues. Thr403, Thr404, Thr424 and Thr438 in the occludin C-terminal domain are the predominant sites of PKC?-dependent phosphorylation. A T424A or T438A mutation in full-length occludin delays its assembly into the tight junctions. Inhibition of PKC? also induces redistribution of occludin and ZO-1 from the tight junctions and dissociates these proteins from the detergent-insoluble fractions in mouse ileum. The present study demonstrates that PKC? phosphorylates occludin on specific threonine residues and promotes assembly of epithelial tight junctions.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1470-8728
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
437
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
289-99
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Protein kinase C? phosphorylates occludin and promotes assembly of epithelial tight junctions.
pubmed:affiliation
Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural