JCB logo
Accuri Cytometers
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 11 July 2005. doi:10.1083/jcb.200409117
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 170, Number 2, 295-304
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 4611K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sunayama, J.
Right arrow Articles by Gotoh, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sunayama, J.
Right arrow Articles by Gotoh, Y.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Article

JNK antagonizes Akt-mediated survival signals by phosphorylating 14-3-3



Jun Sunayama, Fuminori Tsuruta, Norihisa Masuyama, and Yukiko Gotoh

Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan

Correspondence to Yukiko Gotoh: ygotoh{at}iam.u-tokyo.ac.jp

Life and death decisions are made by integrating a variety of apoptotic and survival signals in mammalian cells. Therefore, there is likely to be a common mechanism that integrates multiple signals adjudicating between the alternatives. In this study, we propose that 14-3-3 represents such an integration point. Several proapoptotic proteins commonly become associated with 14-3-3 upon phosphorylation by survival-mediating kinases such as Akt. We reported previously that cellular stresses induce c-Jun NH2-terminal kinase (JNK)–mediated 14-3-3{zeta} phosphorylation at Ser184 (Tsuruta, F., J. Sunayama, Y. Mori, S. Hattori, S. Shimizu, Y. Tsujimoto, K. Yoshioka, N. Masuyama, and Y. Gotoh. 2004. EMBO J. 23:1889–1899). Here, we show that phosphorylation of 14-3-3 by JNK releases the proapoptotic proteins Bad and FOXO3a from 14-3-3 and antagonizes the effects of Akt signaling. As a result of dissociation, Bad is dephosphorylated and translocates to the mitochondria, where it associates with Bcl-2/Bcl-xL. Because Bad and FOXO3a share the 14-3-3–binding motif with other proapoptotic proteins, we propose that this JNK-mediated phosphorylation of 14-3-3 regulates these proapoptotic proteins in concert and makes cells more susceptible to apoptotic signals.

Abbreviations used in this paper: CA, constitutively active; DN, dominant negative; JBD, JNK-binding domain; JNK, c-Jun NH2-terminal kinase; KN, kinase negative; OA, okadaic acid, siRNA, small interference RNA; RNAi, RNA interference; WT, wild type.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents