PMID- 10377409
OWN - NLM
STAT- MEDLINE
DCOM- 19990719
LR  - 20220409
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 13
DP  - 1999 Jun 22
TI  - Ezrin, a plasma membrane-microfilament linker, signals cell survival through the 
      phosphatidylinositol 3-kinase/Akt pathway.
PG  - 7300-5
AB  - 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.
FAU - Gautreau, A
AU  - Gautreau A
AD  - Laboratoire de Morphogenese et Signalisation Cellulaires, Unite Mixte de 
      Recherche, 144 Centre National de la Recherche Scientifique/Institut Curie, 26 
      rue d'Ulm, 75248 Paris Cedex 05, France.
FAU - Poullet, P
AU  - Poullet P
FAU - Louvard, D
AU  - Louvard D
FAU - Arpin, M
AU  - Arpin M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (ezrin)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
SB  - IM
MH  - Actin Cytoskeleton/physiology
MH  - Animals
MH  - Apoptosis/physiology
MH  - Cell Line
MH  - Cell Membrane/physiology
MH  - Cell Survival/physiology
MH  - Cytoskeletal Proteins
MH  - Epithelial Cells/*cytology/*physiology
MH  - Humans
MH  - Kidney/cytology
MH  - Mice
MH  - Mutation
MH  - Phosphatidylinositol 3-Kinases/*physiology
MH  - Phosphoproteins/*physiology
MH  - Rabbits
MH  - Signal Transduction/*physiology
PMC - PMC22080
EDAT- 1999/06/23 00:00
MHDA- 1999/06/23 00:01
PMCR- 1999/12/22
CRDT- 1999/06/23 00:00
PHST- 1999/06/23 00:00 [pubmed]
PHST- 1999/06/23 00:01 [medline]
PHST- 1999/06/23 00:00 [entrez]
PHST- 1999/12/22 00:00 [pmc-release]
AID - 1594 [pii]
AID - 10.1073/pnas.96.13.7300 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7300-5. doi: 
      10.1073/pnas.96.13.7300.