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• W2063403629 startingPage "14469" @default.
• W2063403629 abstract "Atypical protein kinase Cs (PKCs) (aPKCzeta and lambda/iota) have emerged as important binding partners for ceramide, a membrane-resident cell signaling lipid that is involved in the regulation of apoptosis as well as cell polarity. Using ceramide overlay assays with proteolytic fragments of PKCzeta and vesicle binding assays with ectopically expressed protein, we show that a protein fragment comprising the carboxyl-terminal 20-kDa sequence of PKCzeta (C20zeta, amino acids 405-592) bound to C16:0 ceramide. This sequence is not identical to the C1 domain (amino acids 131-180), which has been suggested to serve as a potential ceramide binding domain. Using immunocytochemistry, we found that a C20zeta protein fragment ectopically expressed in two epithelial cell types (neural progenitors and Madin-Darby canine kidney cells) co-distributed with ceramide. Stable expression of C20zeta-EGFP in Madin-Darby canine kidney cells disrupted the formation of adherens and tight junctions and impaired the epithelium integrity by reducing transepithelial electrical resistance. Disruption of cell adhesion and loss of transepithelial electrical resistance was prevented by incubation with C16:0 ceramide. Our results show, for the first time, that there is a novel ceramide binding domain (C20zeta) in the carboxyl terminus of aPKC. Our results also show that the interaction of ceramide with this binding domain is essential for cell-to-cell contacts in epithelia. Therefore, ceramide interaction with the C20zeta binding domain is a potential mechanism by which ceramide and aPKC regulate the formation of junctional complexes in epithelial cells." @default.
• W2063403629 created "2016-06-24" @default.
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• W2063403629 date "2009-05-01" @default.
• W2063403629 modified "2023-10-17" @default.
• W2063403629 title "The Carboxyl-terminal Domain of Atypical Protein Kinase Cζ Binds to Ceramide and Regulates Junction Formation in Epithelial Cells" @default.
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• W2063403629 doi "https://doi.org/10.1074/jbc.m808909200" @default.
• W2063403629 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2682895" @default.
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