Reference - Detail
|Author||Yamanaka T, Horikoshi Y, Suzuki A, Sugiyama Y, Kitamura K, Maniwa R, Nagai Y, Yamashita A, Hirose T, Ishikawa H, Ohno S.|
|Title||PAR-6 regulates aPKC activity in a novel way and mediates cell-cell contact-induced formation of the epithelial junctional complex.|
BACKGROUND:PAR-6, aPKC and PAR-3 are polarity proteins that co-operate in the establishment of cell polarity in Caenorhabditis elegans and Drosophila embryos. We have recently shown that mammalian aPKC is required for the formation of the epithelia-specific cell-cell junctional structure. We have also revealed that a mammalian PAR-6 forms a ternary complex with aPKC and ASIP/PAR-3, and localizes at the most apical end of the junctional complex in epithelial cells.
RESULTS:The ternary complex formation and junctional co-localization of PAR-6 with aPKC and ASIP/PAR-3 are observed during the early stage of epithelial cell polarization. In addition, over-expression of the PAR-6 mutant with CRIB/PDZ domain in MDCK cells disturbs the cell-cell contact-induced junctional localization of tight junction proteins, as well as inhibiting TER development. Furthermore, the binding of Cdc42:GTP to the CRIB/PDZ domain of PAR-6 enhances the kinase activity of PAR-6-bound aPKC. Detailed analyses suggest that the binding of PAR-6 to aPKC has the intrinsic potential to activate aPKC, which is only released when Cdc42:GTP binds to the CRIB/PDZ domain.
CONCLUSION:The results indicate the involvement of PAR-6 in the aPKC function which is required for the cell-cell adhesion-induced formation of epithelial junctional structures, possibly through the cooperative regulation of aPKC activity with Cdc42.
|MeSH||Animals COS Cells Caenorhabditis elegans Caenorhabditis elegans Proteins Carrier Proteins* Cell Adhesion Cell Adhesion Molecules* Cell Communication Cell Line Cell Line, Transformed Cell Polarity Epithelial Cells / cytology Epithelial Cells / metabolism Guanosine Triphosphate / metabolism Helminth Proteins / physiology Humans Intercellular Junctions / physiology* Mutation Protein Binding Protein Kinase C / physiology* Proteins / genetics Proteins / physiology* Signal Transduction Transfection cdc42 GTP-Binding Protein / metabolism|
|WOS Category||GENETICS & HEREDITY CELL BIOLOGY|
|DNA material||pAxCAwt (RDB01678) AxCANLacZ (RDB01749)|