HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE ADVANCED SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Fujii, Y. Articles by Koyasu, S. Search for Related Content PubMed Articles by Fujii, Y. Articles by Koyasu, S.

¹ Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
² Department of Pediatrics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
³ Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo 102-0081, Japan

Nur77 is a nuclear orphan steroid receptor that has been implicated in negative selection when immature T cells are strongly activated through interaction with self peptide-MHC complexes. The expression of Nur77 in thymocytes and T cell lines leads to apoptosis in a manner dependent on its transcriptional activity. It is well established that Nur77 function is negatively regulated by post-translational modification. Here we demonstrate that the MAPK-induced phosphorylation of Nur77 during T cell activation plays a critical role in the induction of apoptosis. Upon T cell receptor (TCR) stimulation, ERK5 (also known as big MAP kinase 1, BMK1), a member of the MAPK family, phosphorylates Nur77, leading to its transcriptional activation. In contrast, the activation of the ERK2 signaling pathway failed to activate Nur77 although ERK2 is also able to phosphorylate Nur77. Furthermore, the blockade of ERK5 signaling pathway suppressed TCR-induced cell death. These results indicate that ERK5 regulates Nur77 function through its phosphorylation.

^aPresent address: Department of Cell Signaling, Institute of Biomedical Science, Kansai Medical University, Moriguchi 570-8506, Japan

^* Correspondence: Email: koyasu{at}sc.itc.keio.ac.jp