PAR-6 regulates aPKC activity in a novel way and mediates cell-cell contact-induced formation of the epithelial junctional complex

Genes Cells. 2001 Aug;6(8):721-31. doi: 10.1046/j.1365-2443.2001.00453.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • COS Cells
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins
  • Carrier Proteins*
  • Cell Adhesion
  • Cell Adhesion Molecules*
  • Cell Communication
  • Cell Cycle Proteins
  • 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


  • Adaptor Proteins, Signal Transducing
  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Cell Adhesion Molecules
  • Cell Cycle Proteins
  • Helminth Proteins
  • Pard3 protein, mouse
  • Proteins
  • par-6 protein, C elegans
  • Guanosine Triphosphate
  • PKC-3 protein
  • Protein Kinase C
  • cdc42 GTP-Binding Protein