| First Author | Harris TL | Year | 2015 |
| Journal | PLoS One | Volume | 10 |
| Issue | 5 | Pages | e0123650 |
| PubMed ID | 25951457 | Mgi Jnum | J:235342 |
| Mgi Id | MGI:5796099 | Doi | 10.1371/journal.pone.0123650 |
| Citation | Harris TL, et al. (2015) Drak2 Does Not Regulate TGF-beta Signaling in T Cells. PLoS One 10(5):e0123650 |
| abstractText | Drak2 is a serine/threonine kinase expressed highest in T cells and B cells. Drak2-/- mice are resistant to autoimmunity in mouse models of type 1 diabetes and multiple sclerosis. Resistance to these diseases occurs, in part, because Drak2 is required for the survival of autoreactive T cells that induce disease. However, the molecular mechanisms by which Drak2 affects T cell survival and autoimmunity are not known. A recent report demonstrated that Drak2 negatively regulated transforming growth factor-beta (TGF-beta) signaling in tumor cell lines. Thus, increased TGF-beta signaling in the absence of Drak2 may contribute to the resistance to autoimmunity in Drak2-/- mice. Therefore, we examined if Drak2 functioned as a negative regulator of TGF-beta signaling in T cells, and whether the enhanced susceptibility to death of Drak2-/- T cells was due to augmented TGF-beta signaling. Using several in vitro assays to test TGF-beta signaling and T cell function, we found that activation of Smad2 and Smad3, which are downstream of the TGF-beta receptor, was similar between wildtype and Drak2-/- T cells. Furthermore, TGF-beta-mediated effects on naive T cell proliferation, activated CD8+ T cell survival, and regulatory T cell induction was similar between wildtype and Drak2-/- T cells. Finally, the increased susceptibility to death in the absence of Drak2 was not due to enhanced TGF-beta signaling. Together, these data suggest that Drak2 does not function as a negative regulator of TGF-beta signaling in primary T cells stimulated in vitro. It is important to investigate and discern potential molecular mechanisms by which Drak2 functions in order to better understand the etiology of autoimmune diseases, as well as to validate the use of Drak2 as a target for therapeutic treatment of these diseases. |
