Interaction of the tumor suppressor PTEN/MMAC with a PDZ domain of MAGI3, a novel membrane-associated guanylate kinase

J Biol Chem. 2000 Jul 14;275(28):21477-85. doi: 10.1074/jbc.M909741199.


PTEN/MMAC is a phosphatase that is mutated in multiple human tumors. PTEN/MMAC dephosphorylates 3-phosphorylated phosphatidylinositol phosphates that activate AKT/protein kinase B (PKB) kinase activity. AKT/PKB is implicated in the inhibition of apoptosis, and cell lines and tumors with mutated PTEN/MMAC show increased AKT/PKB kinase activity and resistance to apoptosis. PTEN/MMAC contains a PDZ domain-binding site, and we show here that the phosphatase binds to a PDZ domain of membrane-associated guanylate kinase with inverted orientation (MAGI) 3, a novel inverted membrane-associated guanylate kinase that localizes to epithelial cell tight junctions. Importantly, MAGI3 and PTEN/MMAC cooperate to modulate the kinase activity of AKT/PKB. These data suggest that MAGI3 allows for the juxtaposition of PTEN/MMAC to phospholipid signaling pathways involved with cell survival.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cell Line
  • Conserved Sequence
  • Epithelial Cells / enzymology
  • Female
  • Genes, Suppressor
  • Guanylate Kinases
  • Humans
  • Male
  • Membrane Proteins
  • Molecular Sequence Data
  • Nucleoside-Phosphate Kinase / chemistry*
  • Nucleoside-Phosphate Kinase / metabolism*
  • Organ Specificity
  • PTEN Phosphohydrolase
  • Phosphoric Monoester Hydrolases / chemistry*
  • Phosphoric Monoester Hydrolases / metabolism*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Tight Junctions / enzymology
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins*


  • MAGI3 protein, human
  • Membrane Proteins
  • Recombinant Proteins
  • Tumor Suppressor Proteins
  • Nucleoside-Phosphate Kinase
  • Guanylate Kinases
  • Phosphoric Monoester Hydrolases
  • PTEN Phosphohydrolase
  • PTEN protein, human