JCB logo
amgmicro.com
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 31 May 2005. doi:10.1083/jcb.200409099
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 169, Number 5, 755-763
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 1252K)
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 Khaled, A. R.
Right arrow Articles by Durum, S. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Khaled, A. R.
Right arrow Articles by Durum, S. K.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*UniGene
*Compound via MeSH
*Substance via MeSH
Related Collections
Right arrowRelated Article
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

Cytokine-driven cell cycling is mediated through Cdc25A



Annette R. Khaled1,3, Dmitry V. Bulavin2, Christina Kittipatarin1, Wen Qing Li3, Michelle Alvarez1, Kyungjae Kim3,5, Howard A. Young4, Albert J. Fornace2, and Scott K. Durum3

1 University of Central Florida, BioMolecular Science Center, Orlando, FL 32628
2 Division of Basic Sciences, National Cancer Institute, Bethesda, MD 20892
3 Laboratory of Molecular Immunoregulation, National Cancer Institute at Frederick, Frederick, MD 21702
4 Laboratory of Experimental Immunology, National Cancer Institute at Frederick, Frederick, MD 21702
5 Department of Pharmacy, Sahm-Yook University, Seoul, Korea, 139-742

Correspondence to Annette R. Khaled: akhaled{at}mail.ucf.edu; or Scott K. Durum: durums{at}mail.ncifcrf.gov

Lymphocytes are the central mediators of the immune response, requiring cytokines for survival and proliferation. Survival signaling targets the Bcl-2 family of apoptotic mediators, however, the pathway for the cytokine-driven proliferation of lymphocytes is poorly understood. Here we show that cytokine-induced cell cycle progression is not solely dependent on the synthesis of cyclin-dependent kinases (Cdks) or cyclins. Rather, we observe that in lymphocyte cell lines dependent on interleukin-3 or interleukin-7, or primary lymphocytes dependent on interleukin 7, the phosphatase Cdc25A is the critical mediator of proliferation. Withdrawal of IL-7 or IL-3 from dependent lymphocytes activates the stress kinase, p38 MAPK, which phosphorylates Cdc25A, inducing its degradation. As a result, Cdk/cyclin complexes remain phosphorylated and inactive and cells arrest before the induction of apoptosis. Inhibiting p38 MAPK or expressing a mutant Cdc25A, in which the two p38 MAPK target sites, S75 and S123, are altered, renders cells resistant to cytokine withdrawal, restoring the activity of Cdk/cyclin complexes and driving the cell cycle independent of a growth stimulus.

Abbreviations used in this paper: DP, dominant-positive; PI, propidium iodide; Rb, Retinoblastoma; RPA, RNase protection assay.


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?

Related Article

Interleukins drive the cell cycle
Rabiya S. Tuma
J. Cell Biol. 2005 169: 700. [Full Text] [PDF]



This article has been cited by other articles:



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