| First Author | Thompson J | Year | 2010 |
| Journal | Eur J Immunol | Volume | 40 |
| Issue | 7 | Pages | 2041-9 |
| PubMed ID | 20411565 | Mgi Jnum | J:165934 |
| Mgi Id | MGI:4838943 | Doi | 10.1002/eji.200940231 |
| Citation | Thompson J, et al. (2010) Protein kinase C regulates mitochondrial targeting of Nur77 and its family member Nor-1 in thymocytes undergoing apoptosis. Eur J Immunol 40(7):2041-9 |
| abstractText | Nur77 orphan steroid receptor and its family member Nor-1 are required for apoptosis of developing T cells. In thymocytes, signals from the TCR complex induce Nur77 and Nor-1 expression followed by translocation from the nucleus to mitochondria. Nur77 and Nor-1 associate with Bcl-2 in the mitochondria, resulting in a conformation change that exposes the Bcl-2 BH3 domain, a presumed pro-apoptotic molecule of Bcl-2. As Nur77 and Nor-1 are heavily phosphorylated, we examined the requirement of Nur77 and Nor-1 phosphorylation in mitochondria translocation and Bcl-2 BH3 exposure. We found that HK434, a PKC agonist, in combination with calcium ionophore, can induce Nur77 and Nor-1 phosphorylation, translocation, Bcl-2 BH3 exposure and thymocyte apoptosis. Inhibitors of both classical and novel forms of PKC were able to block this process. In contrast, only the general but not classical PKC-specific inhibitors were able to block the same process initiated by PMA, a commonly used PKC agonist. These data demonstrate a differential activation of PKC isoforms by PMA and HK434 in thymocytes, and show the importance of PKC in mitochondria translocation of Nur77/Nor-1 and Bcl-2 conformation change during TCR-induced thymocyte apoptosis. |
