| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Institut National de la Santé et de la Recherche Médicale U749, Faculté de Pharmacie, Châtenay-Malabry, France; and
Unité Mixte Recherche 891, Institut National de la Santé et de la Recherche Médicale, Institut Paoli-Calmettes, Marseille, France
Upon engagement by its ligand, the Fas receptor (CD95/APO-1) is oligomerized in a manner dependent on F-actin. It has been shown that ezrin, a member of the ERM (ezrin-radixin-moesin) protein family can link Fas to the actin cytoskeleton. We show herein that in Jurkat cells, not only ezrin but also moesin can associate with Fas. The same observation was made in activated human peripheral blood T cells. Fas/ezrin or moesin (E/M) association increases in Jurkat cells following Fas triggering and occurs concomitantly with the formation of SDS- and 2-ME-stable high molecular mass Fas aggregates. Ezrin and moesin have to be present together for the formation of Fas aggregates since down-regulation of either ezrin or moesin expression with small interfering RNAs completely inhibits Fas aggregate formation. Although FADD (Fas-associated death domain protein) and caspase-8 associate with Fas in the absence of E/M, subsequent events such as caspase-8 activation and sensitivity to apoptosis are decreased. During the course of Fas stimulation, ezrin and moesin become phosphorylated, respectively, on T567 and on T558. This phosphorylation is mediated by the kinase ROCK (Rho-associated coiled coil-containing protein kinase) I subsequently to Rho activation. Indeed, inhibition of either Rho or ROCK prevents ezrin and moesin phosphorylation, abrogates the formation of Fas aggregates, and interferes with caspase-8 activation. Thus, phosphorylation of E/M by ROCK is involved in the early steps of apoptotic signaling following Fas triggering and regulates apoptosis induction.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Institut National de la Santé et de la Recherche Médicale, Ligue Nationale contre le Cancer (équipe labellisée 2006–2009) and Agence Nationale de la Recherche Grant BLAN06-2_135169.
2 S.P. and M.S. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Jocelyne Hamelin, Institut National de la Santé et de la Recherche Médicale (INSERM) U749, Faculté de Pharmacie, 5 rue J. B. Clément, 92290 Châtenay-Malabry, France. E-mail address: jocelyne.hamelin{at}u-psud.fr
4 Abbreviations used in this paper: FADD, Fas-associated death domain protein; AICD, activation-induced cell death; DISC, death-inducing signaling complex; E/M, ezrin or moesin; ERM, ezrin-radixin-moesin; IP, immunoprecipitation; PIP2, phosphatidylinositol 4,5-bisphosphate; RBD, Rho-binding domain of rhotekin; ROCK, Rho-associated coiled coil-containing protein kinase; si, small interfering; WT, wild type.
This article has been cited by other articles:
|
|
 |
|
  X. Guo, L. Wang, B. Chen, Q. Li, J. Wang, M. Zhao, W. Wu, P. Zhu, X. Huang, and Q. Huang ERM protein moesin is phosphorylated by advanced glycation end products and modulates endothelial permeability Am J Physiol Heart Circ Physiol, July 1, 2009; 297(1): H238 - H246. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
