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Science 11 December 1998:
Vol. 282. no. 5396, pp. 2092 - 2095
DOI: 10.1126/science.282.5396.2092
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Reports

Defective T Cell Differentiation in the Absence of Jnk1

Chen Dong, * Derek D. Yang, *dagger Mark Wysk, Alan J. Whitmarsh, Roger J. Davis, Richard A. Flavell ddagger

The c-Jun NH2-terminal kinase (JNK) signaling pathway has been implicated in the immune response that is mediated by the activation and differentiation of CD4 helper T (TH) cells into TH1 and TH2 effector cells. JNK activity observed in wild-type activated TH cells was severely reduced in TH cells from Jnk1-/- mice. The Jnk1-/- T cells hyperproliferated, exhibited decreased activation-induced cell death, and preferentially differentiated to TH2 cells. The enhanced production of TH2 cytokines by Jnk1-/- cells was associated with increased nuclear accumulation of the transcription factor NFATc. Thus, the JNK1 signaling pathway plays a key role in T cell receptor-initiated TH cell proliferation, apoptosis, and differentiation.

C. Dong, D. D. Yang, R. A. Flavell, Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520, USA. M. Wysk, A. J. Whitmarsh, R. J. Davis, Howard Hughes Medical Institute, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
*   These authors contributed equally to this report.

dagger    Present address: Lilly Research Laboratory, Eli Lilly and Co., Indianapolis, IN 46285, USA.

ddagger    To whom correspondence should be addressed. E-mail: richard.flavell{at}qm.yale.edu

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Fibroblast Growth Factor Homologous Factors and the Islet Brain-2 Scaffold Protein Regulate Activation of a Stress-activated Protein Kinase.
J. Schoorlemmer and M. Goldfarb (2002)
J. Biol. Chem. 277, 49111-49119
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JNK1 modulates osteoclastogenesis through both c-Jun phosphorylation-dependent and -independent mechanisms.
J.-P. David, K. Sabapathy, O. Hoffmann, M. H. Idarraga, and E. F. Wagner (2002)
J. Cell Sci. 115, 4317-4325
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In Vivo Role of p38 Mitogen-Activated Protein Kinase in Mediating the Anti-inflammatory Effects of CpG Oligodeoxynucleotide in Murine Asthma.
B. K. Choudhury, J. S. Wild, R. Alam, D. M. Klinman, I. Boldogh, N. Dharajiya, W. J. Mileski, and S. Sur (2002)
J. Immunol. 169, 5955-5961
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ERK5 MAPK Regulates Embryonic Angiogenesis and Acts as a Hypoxia-sensitive Repressor of Vascular Endothelial Growth Factor Expression.
S. J. Sohn, B. K. Sarvis, D. Cado, and A. Winoto (2002)
J. Biol. Chem. 277, 43344-43351
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Phenylethyl Isothiocyanate Induces Apoptotic Signaling via Suppressing Phosphatase Activity against c-Jun N-terminal Kinase.
Y.-R. Chen, J. Han, R. Kori, A.-N. T. Kong, and T.-H. Tan (2002)
J. Biol. Chem. 277, 39334-39342
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Disruption of Mekk2 in Mice Reveals an Unexpected Role for MEKK2 in Modulating T-Cell Receptor Signal Transduction.
Z. Guo, G. Clydesdale, J. Cheng, K. Kim, L. Gan, D. J. McConkey, S. E. Ullrich, Y. Zhuang, and B. Su (2002)
Mol. Cell. Biol. 22, 5761-5768
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Ras Activation in T Cells Determines the Development of Antigen-Induced Airway Hyperresponsiveness and Eosinophilic Inflammation.
Y. Shibata, T. Kamata, M. Kimura, M. Yamashita, C.-R. Wang, K. Murata, M. Miyazaki, M. Taniguchi, N. Watanabe, and T. Nakayama (2002)
J. Immunol. 169, 2134-2140
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Induction of experimental autoimmune encephalomyelitis in the absence of c-Jun N-terminal kinase 2.
K. Nicolson, S. Freland, C. Weir, B. Delahunt, R. A. Flavell, and B. T. Backstrom (2002)
Int. Immunol. 14, 849-856
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Th1/Th2 cell differentiation of developing CD4 single-positive thymocytes.
E. Kikkawa, M. Yamashita, M. Kimura, M. Omori, K. Sugaya, C. Shimizu, T. Katsumoto, M. Ikekita, M. Taniguchi, and T. Nakayama (2002)
Int. Immunol. 14, 943-951
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Cbl-b Positively Regulates Btk-mediated Activation of Phospholipase C-{gamma}2 in B Cells.
T. Yasuda, T. Tezuka, A. Maeda, T. Inazu, Y. Yamanashi, H. Gu, T. Kurosaki, and T. Yamamoto (2002)
J. Exp. Med. 196, 51-63
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Phosphorylation of NFATc4 by p38 Mitogen-Activated Protein Kinases.
T. T. C. Yang, Q. Xiong, H. Enslen, R. J. Davis, and C.-W. Chow (2002)
Mol. Cell. Biol. 22, 3892-3904
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A co-stimulatory molecule on activated T cells, H4/ICOS, delivers specific signals in Th cells and regulates their responses.
Y. Arimura, H. Kato, U. Dianzani, T. Okamoto, S. Kamekura, D. Buonfiglio, T. Miyoshi-Akiyama, T. Uchiyama, and J. Yagi (2002)
Int. Immunol. 14, 555-566
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Targets of c-Jun NH2-terminal Kinase 2-mediated Tumor Growth Regulation Revealed by Serial Analysis of Gene Expression.
O. Potapova, S. V. Anisimov, M. Gorospe, R. H. Dougherty, W. A. Gaarde, K. R. Boheler, and N. J. Holbrook (2002)
Cancer Res. 62, 3257-3263
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Differential Gene Expression Profiles of Jnk1- and Jnk2-deficient Murine Fibroblast Cells.
N. Chen, Q.-B. She, A. M. Bode, and Z. Dong (2002)
Cancer Res. 62, 1300-1304
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Deficiency of c-Jun-NH2-terminal Kinase-1 in Mice Enhances Skin Tumor Development by 12-O-Tetradecanoylphorbol-13-Acetate.
Q.-B. She, N. Chen, A. M. Bode, R. A. Flavell, and Z. Dong (2002)
Cancer Res. 62, 1343-1348
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Distinct Role of p38 and c-Jun N-Terminal Kinases in IL-10-Dependent and IL-10-Independent Regulation of the Costimulatory Molecule B7.2 in Lipopolysaccharide-Stimulated Human Monocytic Cells.
W. Lim, W. Ma, K. Gee, S. Aucoin, D. Nandan, F. Diaz-Mitoma, M. Kozlowski, and A. Kumar (2002)
J. Immunol. 168, 1759-1769
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Direct Activation of Mitogen-Activated Protein Kinase Kinase Kinase MEKK1 by the Ste20p Homologue GCK and the Adapter Protein TRAF2.
D. N. Chadee, T. Yuasa, and J. M. Kyriakis (2002)
Mol. Cell. Biol. 22, 737-749
   Abstract »    Full Text »    PDF »


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