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

Xinyi Wu, Karin Hepner, Shobha Castelino-Prabhu, Duc Do, Marc B. Kaye, Xiu Juan Yuan, Jonathan Wood, Christopher A Ross, Charles L. Sawyers, Young E. Whang

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)4233-4238
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number8
DOIs
StatePublished - Apr 11 2000

Fingerprint

Guanylate Kinases
PDZ Domains
Membranes
Neoplasms
Proteins
Protein Interaction Domains and Motifs
Multiprotein Complexes
Two-Hybrid System Techniques
Tight Junctions
Protein C
Tumor Suppressor Genes
Phosphoric Monoester Hydrolases
Epithelial Cells
Cell Membrane
Mutation

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Evidence for regulation of the PTEN tumor suppressor by a membrane- localized multi-PDZ domain containing scaffold protein MAGI-2. / Wu, Xinyi; Hepner, Karin; Castelino-Prabhu, Shobha; Do, Duc; Kaye, Marc B.; Yuan, Xiu Juan; Wood, Jonathan; Ross, Christopher A; Sawyers, Charles L.; Whang, Young E.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 8, 11.04.2000, p. 4233-4238.

Research output: Contribution to journalArticle

Wu, Xinyi ; Hepner, Karin ; Castelino-Prabhu, Shobha ; Do, Duc ; Kaye, Marc B. ; Yuan, Xiu Juan ; Wood, Jonathan ; Ross, Christopher A ; Sawyers, Charles L. ; Whang, Young E. / Evidence for regulation of the PTEN tumor suppressor by a membrane- localized multi-PDZ domain containing scaffold protein MAGI-2. In: Proceedings of the National Academy of Sciences of the United States of America. 2000 ; Vol. 97, No. 8. pp. 4233-4238.
@article{0165b2ae98c64d5e815be4f71c60a478,
title = "Evidence for regulation of the PTEN tumor suppressor by a membrane- localized multi-PDZ domain containing scaffold protein MAGI-2",
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.",
author = "Xinyi Wu and Karin Hepner and Shobha Castelino-Prabhu and Duc Do and Kaye, {Marc B.} and Yuan, {Xiu Juan} and Jonathan Wood and Ross, {Christopher A} and Sawyers, {Charles L.} and Whang, {Young E.}",
year = "2000",
month = "4",
day = "11",
doi = "10.1073/pnas.97.8.4233",
language = "English (US)",
volume = "97",
pages = "4233--4238",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "8",

}

TY - JOUR

T1 - Evidence for regulation of the PTEN tumor suppressor by a membrane- localized multi-PDZ domain containing scaffold protein MAGI-2

AU - Wu, Xinyi

AU - Hepner, Karin

AU - Castelino-Prabhu, Shobha

AU - Do, Duc

AU - Kaye, Marc B.

AU - Yuan, Xiu Juan

AU - Wood, Jonathan

AU - Ross, Christopher A

AU - Sawyers, Charles L.

AU - Whang, Young E.

PY - 2000/4/11

Y1 - 2000/4/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0034636038&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034636038&partnerID=8YFLogxK

U2 - 10.1073/pnas.97.8.4233

DO - 10.1073/pnas.97.8.4233

M3 - Article

VL - 97

SP - 4233

EP - 4238

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 8

ER -