Interaction of the Tumor Suppressor PTEN/MMAC with a PDZ Domain of MAGI3, a Novel Membrane-associated Guanylate Kinase
| Autor: | Yan Wu, Laurence A. Lasky, Qimin Gu, Richard P. Laura, Susan D. Spencer, James Lee, Donald Dowbenko |
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| Rok vydání: | 2000 |
| Předmět: |
Male
Guanylate kinase Molecular Sequence Data Phosphatase PDZ domain Saccharomyces cerevisiae Membrane-associated guanylate kinase Biochemistry Cell Line Tight Junctions Tumor Cells Cultured Animals Humans PTEN Amino Acid Sequence Kinase activity Genes Suppressor Molecular Biology Protein kinase B Conserved Sequence Binding Sites Sequence Homology Amino Acid biology Chemistry Tumor Suppressor Proteins PTEN Phosphohydrolase Membrane Proteins Epithelial Cells Cell Biology Phosphoric Monoester Hydrolases Recombinant Proteins Organ Specificity Cancer research biology.protein Female Signal transduction Nucleoside-Phosphate Kinase Guanylate Kinases Sequence Alignment |
| Zdroj: | Journal of Biological Chemistry. 275:21477-21485 |
| ISSN: | 0021-9258 |
| Popis: | 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 ofmembrane-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. |
| Databáze: | OpenAIRE |
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