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Molecular and Cellular Biology, September 2003, p. 6442-6454, Vol. 23, No. 18
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.18.6442-6454.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Nuclear Factor of Activated T Cells c Is a Target of p38 Mitogen-Activated Protein Kinase in T Cells

Chia-Cheng Wu,1,2 Shu-Ching Hsu,2 Hsiu-ming Shih,3 and Ming-Zong Lai1,2,4*

Graduate Institute of Immunology, School of Medicine, National Taiwan University,1 Institute of Molecular Biology, Academia Sinica,2 Division of Molecular and Genomic Medicine, National Health Research Institute,3 Graduate Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan, Republic of China4

Received 6 December 2002/ Returned for modification 16 January 2003/ Accepted 17 June 2003

p38 mitogen activated protein kinase (MAPK) is essential for T-cell activation. Here we demonstrated that nuclear factor of activated T cells (NFAT) is a direct target of p38 MAPK. Inhibition of p38 MAPK led to selective inactivation of NFAT in T cells. We further linked a strict requirement of p38 MAPK to activation of NFATc. A stimulatory effect of p38 MAPK on at least four other stages of NFATc activation was found. First, the p38 MAPK cascade activated the NFATc promoter and induced the transcription of NFATc mRNA. Second, p38 MAPK mildly increased the mRNA stability of NFATc. Third, p38 MAPK enhanced the translation of NFATc mRNA. Fourth, p38 MAPK promoted the interaction of NFATc with the coactivator CREB-binding protein. In contrast, p38 MAPK moderately enhanced the expulsion of NFATc from the nucleus in T cells. Therefore, p38 MAPK has opposite effects on different stages of NFATc activation. All together, the overall effect of p38 MAPK on NFATc in T cells is clear activation.

* Corresponding author. Mailing address: Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 11529, Taiwan, Republic of China. Phone: (886)-2-2789-9236. Fax: (886)-2-2782-6085. E-mail: mblai{at}ccvax.sinica.edu.tw.

Molecular and Cellular Biology, September 2003, p. 6442-6454, Vol. 23, No. 18
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.18.6442-6454.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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