A Mammalian PAR-3-PAR-6 Complex Implicated in Cdc42/Rac1 and aPKC Signalling and Cell Polarity

Nat Cell Biol. 2000 Aug;2(8):540-7. doi: 10.1038/35019582.

Abstract

Cellular asymmetry is critical for the development of multicellular organisms. Here we show that homologues of proteins necessary for asymmetric cell division in Caenorhabditis elegans associate with each other in mammalian cells and tissues. mPAR-3 and mPAR-6 exhibit similar expression patterns and subcellular distributions in the CNS and associate through their PDZ (PSD-95/Dlg/ZO-1) domains. mPAR-6 binds to Cdc42/Rac1 GTPases, and mPAR-3 and mPAR-6 bind independently to atypical protein kinase C (aPKC) isoforms. In vitro, mPAR-3 acts as a substrate and an inhibitor of aPKC. We conclude that mPAR-3 and mPAR-6 have a scaffolding function, coordinating the activities of several signalling proteins that are implicated in mammalian cell polarity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Brain / metabolism
  • Caenorhabditis elegans Proteins*
  • Cell Fractionation
  • Cell Line
  • Cell Polarity*
  • Cloning, Molecular
  • Enzyme Activation
  • Helminth Proteins / chemistry
  • Helminth Proteins / genetics
  • Helminth Proteins / metabolism*
  • Immunohistochemistry
  • Macromolecular Substances
  • Mice
  • Mutation
  • Phosphorylation
  • Precipitin Tests
  • Protein Binding
  • Protein Isoforms / antagonists & inhibitors
  • Protein Isoforms / chemistry
  • Protein Isoforms / metabolism
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / chemistry
  • Protein Kinase C / metabolism*
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases
  • Proteins / chemistry
  • Proteins / genetics
  • Proteins / metabolism*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction*
  • Transfection
  • cdc42 GTP-Binding Protein / chemistry
  • cdc42 GTP-Binding Protein / genetics
  • cdc42 GTP-Binding Protein / metabolism*
  • rac1 GTP-Binding Protein / chemistry
  • rac1 GTP-Binding Protein / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • Helminth Proteins
  • Macromolecular Substances
  • Protein Isoforms
  • Proteins
  • Recombinant Fusion Proteins
  • par-6 protein, C elegans
  • PAR-3 protein, C elegans
  • Protein-Serine-Threonine Kinases
  • PKC-3 protein
  • Protein Kinase C
  • cdc42 GTP-Binding Protein
  • rac1 GTP-Binding Protein