title: Ezrin, a plasma membrane-microfilament linker, signals cell survival through the phosphatidylinositol 3-kinase/Akt pathway.
abstract: 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.
authors.affiliation: Laboratoire de Morphogenèse et Signalisation Cellulaires, Unité Mixte de Recherche, 144 Centre National de la Recherche Scientifique/Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France.
authors.forename: A
authors.initials: A
authors.lastname: Gautreau
authors.forename: P
authors.initials: P
authors.lastname: Poullet
authors.forename: D
authors.initials: D
authors.lastname: Louvard
authors.forename: M
authors.initials: M
authors.lastname: Arpin
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D003598:Cytoskeletal Proteins; D004847:Epithelial Cells / Q000166:cytology* / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000166:cytology; D051379:Mice; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D010750:Phosphoproteins / Q000502:physiology*; D011817:Rabbits; D015398:Signal Transduction / Q000502:physiology*; D000099149:Ezrin
chemical_list: D003598:Cytoskeletal Proteins; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D000099149:Ezrin