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A Constitutively Nuclear Form of NFATx Shows Efficient Transactivation Activity and Induces Differentiation of CD4+CD8+ T Cells

Amasaki, Yoshiharu and Adachi, Satoko and Ishida, Yukisato and Iwata, Makoto and Arai, Naoko and Arai, Ken-ichi and Miyatake, Shoichiro (2002) A Constitutively Nuclear Form of NFATx Shows Efficient Transactivation Activity and Induces Differentiation of CD4+CD8+ T Cells. Journal of Biological Chemistry, 277 (28). pp. 25640-25648. ISSN 0021-9258. http://resolver.caltech.edu/CaltechAUTHORS:AMAjbc02

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Abstract

The Ca2+ signal facilitates nuclear translocation of NFAT through the dephosphorylation of clustered serine residues in the calcium regulatory domain by the Ca2+/calmodulin-dependent phosphatase calcineurin. The conformation of dephosphorylated NFAT exposes the nuclear localization signal for translocation into the nucleus and masks the nuclear export sequence to keep the protein in the nucleus. It has been reported that deletion of some serine-rich motifs masking the nuclear localization signal results in the translocation of NFAT into the nucleus, but that the nuclear export sequence located at the N terminus also needs to be deleted for NFATx (NFAT4/NFATc3) to exert efficient transactivation function. Here, we report that deletion of the critical serine-rich motifs of NFATx leads to a conformation that efficiently exposes the nuclear localization signal and that has stronger transcription activity compared with the fully activated wild-type protein in the presence of the nuclear export sequence. This also suggests that the regulation of the transactivation domain by phosphorylation observed in NFAT1 may not contribute significantly to the transcription activity of NFATx. The expression of this constitutively nuclear form of NFATx in the CD4+CD8+ T cell line facilitates differentiation into the CD4 single-positive stage upon stimulation with phorbol ester. Our data suggest that NFATx is involved in the regulation of co-receptor expression during differentiation into the CD4 single-positive stage.


Item Type:Article
Additional Information:© 2002 by The American Society for Biochemistry and Molecular Biology, Inc. Received for publication, February 25, 2002, and in revised form, April 29, 2002. Originally published In Press as doi:10.1074/jbc.M201860200 on May 7, 2002. A more recent version of this article appeared on July 5, 2002. We thank Dr. K. Maruyama (Tokyo Medical and Dental University) for kindly supplying the pMKIT-Neo plasmid. We thank Drs. Yumiko Kamogawa and Esteban S. Masuda for helpful discussion. We also thank Miho Nagoya for technical assistance.
Subject Keywords:TRANSCRIPTION FACTOR NFAT1; SIGNAL-TRANSDUCTION PATHWAY; POSITIVE SELECTION; NEGATIVE SELECTION; CYCLOSPORINE-A; THYMOCYTE DIFFERENTIATION; IN-VITRO; KAPPA-B; NF-ATC; CALCINEURIN
Record Number:CaltechAUTHORS:AMAjbc02
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:AMAjbc02
Alternative URL:http://dx.doi.org/10.1074/jbc.M201860200
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:3635
Collection:CaltechAUTHORS
Deposited By: Lindsay Cleary
Deposited On:22 Jun 2006
Last Modified:26 Dec 2012 08:55

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