Novel Mechanism of PTEN Regulation by Its Phosphatidylinositol 4,5-Bisphosphate Binding Motif Is Critical for Chemotaxis

Miho Iijima, Yi Elaine Huang, Hongbo R. Luo, Francisca Vazquez, Peter N. Devreotes

Research output: Contribution to journalArticle

Abstract

In chemotaxing cells, localization of phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) to the leading edge of the cell sets the direction and regulates the formation of pseudopods at the anterior. We show that the lipid phosphatase activity of PTEN mediates chemotaxis and that the sharp localization of PI(3,4,5)P3 requires localization of PTEN to the rear of the cell. Our data suggest that a phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) binding motif at the N terminus of PTEN serves the dual role of localizing the enzyme to the membrane and regulating its activity. Mutations in this motif enhance catalytic activity but render the enzyme inactive in vivo by preventing membrane association. The key role of this motif may explain the heretofore puzzling tumor-suppressing mutations occurring within the PI(4,5)P2 binding motif. On the other hand, the localization of PTEN does not depend on its phosphatase activity, the actin cytoskeleton, or the intracellular level of PI(3,4,5)P3, suggesting that events controlling localization are upstream of phosphoinositide signaling.

Original languageEnglish (US)
Pages (from-to)16606-16613
Number of pages8
JournalJournal of Biological Chemistry
Volume279
Issue number16
DOIs
StatePublished - Apr 16 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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