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

Abstract

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.

• Authors: Y Wu, D Dowbenko, S Spencer, R Laura, J Lee, Q Gu, L A Lasky
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 275 Issue 28 Pg. 21477-85 (Jul 14 2000) ISSN: 0021-9258 [Print] United States
• PMID: 10748157 (Publication Type: Journal Article)

Chemical References

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

Topics

• 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, metabolism)
• Organ Specificity
• PTEN Phosphohydrolase
• Phosphoric Monoester Hydrolases (chemistry, metabolism)
• Recombinant Proteins (chemistry, metabolism)
• Saccharomyces cerevisiae
• Sequence Alignment
• Sequence Homology, Amino Acid
• Tight Junctions (enzymology)
• Tumor Cells, Cultured
• Tumor Suppressor Proteins