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

Overview

MeSH Major

  • Apoptosis
  • Apoptosis Regulatory Proteins
  • Carcinoma, Non-Small-Cell Lung
  • Drug Resistance, Neoplasm
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Lung Neoplasms
  • Membrane Proteins
  • Polymorphism, Genetic
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Sequence Deletion

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.

publication date

  • April 11, 2000

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.1073/pnas.97.8.4233

PubMed ID

  • 10760291

Additional Document Info

start page

  • 4233

end page

  • 8

volume

  • 97

number

  • 8