ERK5 is involved in TCR‐induced apoptosis through the modification of Nur77
Open Access
- 21 April 2008
- journal article
- Published by Wiley in Genes to Cells
- Vol. 13 (5), 411-419
- https://doi.org/10.1111/j.1365-2443.2008.01177.x
Abstract
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.Keywords
This publication has 44 references indexed in Scilit:
- Spatiotemporal Regulation of c-Fos by ERK5 and the E3 Ubiquitin Ligase UBR1, and Its Biological RoleMolecular Cell, 2006
- Activation of gp130 Transduces Hypertrophic Signal Through Interaction of Scaffolding/Docking Protein Gab1 With Tyrosine Phosphatase SHP2 in CardiomyocytesCirculation Research, 2003
- Akt Inhibits the Orphan Nuclear Receptor Nur77 and T-cell ApoptosisOnline Journal of Public Health Informatics, 2001
- Induction of Egr-1 expression by the retinoid AHPN in human lung carcinoma cells is dependent on activated ERK1/2Cell Death & Differentiation, 2001
- Nur77 transcription activity correlates with its apoptotic functionin vivoEuropean Journal of Immunology, 1999
- A role for the orphan steroid receptor Nur77 in apoptosis accompanying antigen-induced negative selectionImmunity, 1995
- The MAP kinase cascade is essential for diverse signal transduction pathwaysTrends in Biochemical Sciences, 1993
- Purification and characterization of the 90‐kDa heat‐shock protein from mammalian tissuesJBIC Journal of Biological Inorganic Chemistry, 1988
- Purification and characterization of the 90-kDa heat-shock protein from mammalian tissuesJBIC Journal of Biological Inorganic Chemistry, 1988
- Selective extraction of polyoma DNA from infected mouse cell culturesJournal of Molecular Biology, 1967