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Molecular and Cellular Biology, July 2000, p. 5227-5234, Vol. 20, No. 14
Howard Hughes Medical Institute, Program in Molecular
Medicine, Department of Biochemistry and Molecular Biology, University
of Massachusetts Medical School, Worcester, Massachusetts
01605,1 and Howard Hughes Medical
Institute, Section of Immunobiology, Yale University School of
Medicine, New Haven, Connecticut 065202
Received 10 January 2000/Returned for modification 24 February
2000/Accepted 12 April 2000
The protein phosphatase calcineurin is a critical mediator of
calcium signals during T-cell activation. One substrate of calcineurin is the transcription factor NFATc1, which is retained in the cytoplasm of quiescent cells. NFATc1 activation requires the translocation of the
transcription factor into the nucleus, a process that is mediated by
calcineurin. This interaction with calcineurin requires a targeting
domain (PxIxIT motif) located in the NH2-terminal region of
NFATc1. Here we demonstrate that the calcineurin targeting domain of
NFATc1 is phosphorylated and inactivated by the c-Jun NH2-terminal kinase (JNK). This disruption of calcineurin
targeting inhibits the nuclear accumulation and transcription activity
of NFATc1 and accounts for the observation that
Jnk1
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
c-Jun NH2-Terminal Kinase Inhibits
Targeting of the Protein Phosphatase Calcineurin to NFATc1
/
T cells exhibit greatly increased
NFATc1-dependent nuclear responses.
*
Corresponding author. Mailing address: Howard
Hughes Medical Institute Program in Molecular Medicine University
of Massachusetts Medical School, 373 Plantation St., Worcester, MA
01605. Phone: (508) 856-6054. Fax: (508) 856-3210. E-mail:
Roger.Davis{at}Umassmed.Edu.
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