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Ezrin, a plasma membrane-microfilament linker, signals cell survival through the phosphatidylinositol 3-kinase/Akt pathway.

ERM (Ezrin-Radixin-Moesin) proteins function as plasma membrane-actin cytoskeleton linkers and participate in the formation of specialized domains of the plasma membrane. We have investigated ezrin function in tubulogenesis of a kidney-derived epithelial cell line, LLC-PK1. Here we show that cells overproducing a mutant form of ezrin in which Tyr-353 was changed to a phenylalanine (Y353F) undergo apoptosis when assayed for tubulogenesis. While investigating the mechanism responsible for this apoptosis, we found that ezrin interacts with p85, the regulatory subunit of phosphatidylinositol 3-kinase (PI 3-kinase). Two distinct sites of ezrin are involved in this interaction, the amino-terminal domain containing the first 309 aa and the phosphorylated Tyr-353 residue, which binds to the carboxyl-terminal SH2 domain of p85. Cells producing Y353F ezrin are defective in activation of the protein kinase Akt, a downstream target of PI 3-kinase that protects cells against apoptosis. Furthermore, the apoptotic phenotype of these cells is rescued by production of a constitutively activated form of PI 3-kinase. Taken together, these results establish a novel function for ezrin in determining survival of epithelial cells by activating the PI 3-kinase/Akt pathway.

Pubmed ID: 10377409

Authors

  • Gautreau A
  • Poullet P
  • Louvard D
  • Arpin M

Journal

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

Publication Data

June 22, 1999

Associated Grants

None

Mesh Terms

  • Actin Cytoskeleton
  • Animals
  • Apoptosis
  • Cell Line
  • Cell Membrane
  • Cell Survival
  • Cytoskeletal Proteins
  • Epithelial Cells
  • Humans
  • Kidney
  • Mice
  • Mutation
  • Phosphatidylinositol 3-Kinases
  • Phosphoproteins
  • Rabbits
  • Signal Transduction