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Science 19 June 1998:
Vol. 280. no. 5371, pp. 1945 - 1949
DOI: 10.1126/science.280.5371.1945
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Reports

Stabilization of Interleukin-2 mRNA by the c-Jun NH2-Terminal Kinase Pathway

Ching-Yi Chen, Fabienne Del Gatto-Konczak, Zhenguo Wu, Michael Karin *

Signaling pathways that stabilize interleukin-2 (IL-2) messenger RNA (mRNA) in activated T cells were examined. IL-2 mRNA contains at least two cis elements that mediated its stabilization in response to different signals, including activation of c-Jun amino-terminal kinase (JNK). This response was mediated through a cis element encompassing the 5' untranslated region (UTR) and the beginning of the coding region. IL-2 transcripts lacking this 5' element no longer responded to JNK activation but were still responsive to other signals generated during T cell activation, which were probably sensed through the 3' UTR. Thus, multiple elements within IL-2 mRNA modulate its stability in a combinatorial manner, and the JNK pathway controls turnover as well as synthesis of IL-2 mRNA.

Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
*   To whom correspondence should be addressed.

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C-Jun Nh2-Terminal Kinase (Jnk)1 and Jnk2 Have Similar and Stage-Dependent Roles in Regulating T Cell Apoptosis and Proliferation.
K. Sabapathy, T. Kallunki, J.-P. David, I. Graef, M. Karin, and E. F. Wagner (2001)
J. Exp. Med. 193, 317-328
   Abstract »    Full Text »    PDF »
Regulatory Defects in Cbl and Mitogen-Activated Protein Kinase (Extracellular Signal-Related Kinase) Pathways Cause Persistent Hyperexpression of CD40 Ligand in Human Lupus T Cells.
Y. Yi, M. McNerney, and S. K. Datta (2000)
J. Immunol. 165, 6627-6634
   Abstract »    Full Text »    PDF »
Enhancement of T Cell Receptor Signaling by a Mild Oxidative Shift in the Intracellular Thiol Pool.
S. P. Hehner, R. Breitkreutz, G. Shubinsky, H. Unsoeld, K. Schulze-Osthoff, M. L. Schmitz, and W. Droge (2000)
J. Immunol. 165, 4319-4328
   Abstract »    Full Text »    PDF »
Identification of a Complex that Binds to the CD154 3' Untranslated Region: Implications for a Role in Message Stability During T Cell Activation.
B. Barnhart, P. A. Kosinski, Z. Wang, G. S. Ford, M. Kiledjian, and L. R. Covey (2000)
J. Immunol. 165, 4478-4486
   Abstract »    Full Text »    PDF »
CD28 Utilizes Vav-1 to Enhance TCR-Proximal Signaling and NF-AT Activation.
F. Michel, G. Mangino, G. Attal-Bonnefoy, L. Tuosto, A. Alcover, A. Roumier, D. Olive, and O. Acuto (2000)
J. Immunol. 165, 3820-3829
   Abstract »    Full Text »    PDF »
Lipopolysaccharide induces Jun N-terminal kinase activation in macrophages by a novel Cdc42/Rac-independent pathway involving sequential activation of protein kinase C zeta and phosphatidylcholine-dependent phospholipase C.
K. J. Procyk, M. R. Rippo, R. Testi, F. Hofmann, P. J. Parker, and M. Baccarini (2000)
Blood 96, 2592-2598
   Abstract »    Full Text »    PDF »
The stress-activated MAP kinase Sty1/Spc1 and a 3'-regulatory element mediate UV-induced expression of the uvi15+ gene at the post-transcriptional level.
M. Kim, W. Lee, J. Park, J. B. Kim, Y. K. Jang, R. H. Seong, S. Y. Choe, and S. D. Park (2000)
Nucleic Acids Res. 28, 3392-3402
   Abstract »    Full Text »    PDF »
Redundant and Opposing Functions of Two Tyrosine Kinases, Btk and Lyn, in Mast Cell Activation.
Y. Kawakami, J. Kitaura, A. B. Satterthwaite, R. M. Kato, K. Asai, S. E. Hartman, M. Maeda-Yamamoto, C. A. Lowell, D. J. Rawlings, O. N. Witte, et al. (2000)
J. Immunol. 165, 1210-1219
   Abstract »    Full Text »    PDF »
p38 and Extracellular Signal-Regulated Kinases Regulate the Myogenic Program at Multiple Steps.
Z. Wu, P. J. Woodring, K. S. Bhakta, K. Tamura, F. Wen, J. R. Feramisco, M. Karin, J. Y. J. Wang, and P. L. Puri (2000)
Mol. Cell. Biol. 20, 3951-3964
   Abstract »    Full Text »
UV-Induced Stabilization of c-fos and Other Short-Lived mRNAs.
C. Blattner, P. Kannouche, M. Litfin, K. Bender, H. J. Rahmsdorf, J. F. Angulo, and P. Herrlich (2000)
Mol. Cell. Biol. 20, 3616-3625
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Nucleolin and YB-1 are required for JNK-mediated interleukin-2 mRNA stabilization during T-cell activation.
C.-Y. Chen, R. Gherzi, J. S. Andersen, G. Gaietta, K. Jürchott, H.-D. Royer, M. Mann, and M. Karin (2000)
Genes & Dev. 14, 1236-1248
   Abstract »    Full Text »
IFN-{gamma} and TNF Regulate Macrophage Expression of the Chemotactic S100 Protein S100A8.
K. Xu and C. L. Geczy (2000)
J. Immunol. 164, 4916-4923
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Stability of the ATF2 Transcription Factor Is Regulated by Phosphorylation and Dephosphorylation.
S. Y. Fuchs, I. Tappin, and Z.'e. Ronai (2000)
J. Biol. Chem. 275, 12560-12564
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Interleukin-1-mediated Stabilization of Mouse KC mRNA Depends on Sequences in both 5'- and 3'-Untranslated Regions.
J. M. Tebo, S. Datta, R. Kishore, M. Kolosov, J. A. Major, Y. Ohmori, and T. A. Hamilton (2000)
J. Biol. Chem. 275, 12987-12993
   Abstract »    Full Text »    PDF »
Inhibition of Ikappa B Kinase Activity by Sodium Salicylate in Vitro Does Not Reflect Its Inhibitory Mechanism in Intact Cells.
D. Alpert and J. Vilcek (2000)
J. Biol. Chem. 275, 10925-10929
   Abstract »    Full Text »    PDF »
Urokinase Plasminogen Activator/Urokinase-specific Surface Receptor Expression and Matrix Invasion by Breast Cancer Cells Requires Constitutive p38alpha Mitogen-activated Protein Kinase Activity.
S. Huang, L. New, Z. Pan, J. Han, and G. R. Nemerow (2000)
J. Biol. Chem. 275, 12266-12272
   Abstract »    Full Text »    PDF »
Reconstitution of Angiotensin Receptor mRNA Down-regulation in Vascular Smooth Muscle. POST-TRANSCRIPTIONAL CONTROL BY PROTEIN KINASE A BUT NOT MITOGENIC SIGNALING DIRECTED BY THE 5'-UNTRANSLATED REGION.
K. Xu and T. J. Murphy (2000)
J. Biol. Chem. 275, 7604-7611
   Abstract »    Full Text »    PDF »
Transforming Growth Factor-beta 1 Enhances Ha-ras-induced Expression of Cyclooxygenase-2 in Intestinal Epithelial Cells via Stabilization of mRNA.
H. Sheng, J. Shao, D. A. Dixon, C. S. Williams, S. M. Prescott, R. N. DuBois, and R. D. Beauchamp (2000)
J. Biol. Chem. 275, 6628-6635
   Abstract »    Full Text »    PDF »


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