NDLI: Evidence for regulation of the PTEN tumor suppressor by a membrane-localized multi-PDZ domain containing scaffold protein MAGI-2.

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Evidence for regulation of the PTEN tumor suppressor by a membrane-localized multi-PDZ domain containing scaffold protein MAGI-2.

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Evidence for regulation of the PTEN tumor suppressor by a membrane-localized multi-PDZ domain containing scaffold protein MAGI-2.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Wu, X. Hepner, K. Whang, Y. E. Do, D. Kaye, M. B. Ross, C. Sawyers, C. L. Castelino-prabhu, S. Wood, J. Yuan, X. J.
Description	Author Affiliation: Wu X ( Department of Medicine, Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.);
Abstract	PTEN is a tumor suppressor gene mutated in human cancers. Although many mutations target the phosphatase domain, others create a truncated protein lacking the C-terminal PDZ-binding motif or a protein that extends beyond the PDZ-binding motif. Using the yeast two-hybrid system, we isolated a membrane-associated guanylate kinase family protein with multiple PDZ domains [AIP-1 (atrophin interacting protein 1), renamed MAGI-2 (membrane associated guanylate kinase inverted-2)]. MAGI-2 contains eight potential protein-protein interaction domains and is localized to tight junctions in the membrane of epithelial cells. PTEN binds to MAGI-2 through an interaction between the PDZ-binding motif of PTEN and the second PDZ domain of MAGI-2. MAGI-2 enhances the ability of PTEN to suppress Akt activation. Furthermore, certain PTEN mutants have reduced stability, which is restored by adding the minimal PDZ-binding motif back to the truncated protein. We propose that MAGI-2 improves the efficiency of PTEN signaling through assembly of a multiprotein complex at the cell membrane.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	8
Volume Number	97
Language	English
Publisher	National Academy of Sciences
Publisher Date	2000-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Gene Expression Regulation Genetics Genes, Tumor Suppressor Membrane Proteins Nucleoside-Phosphate Kinase Phosphoric Monoester Hydrolases Proto-Oncogene Proteins Tumor Suppressor Proteins Guanylate Kinase Metabolism PTEN Phosphohydrolase Protein Binding Protein-Serine-Threonine Kinases Antagonists & Inhibitors Proto-Oncogene Proteins C-akt Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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