| First Author | Swan KA | Year | 1995 |
| Journal | EMBO J | Volume | 14 |
| Issue | 2 | Pages | 276-85 |
| PubMed ID | 7835338 | Mgi Jnum | J:132210 |
| Mgi Id | MGI:3775475 | Doi | 10.1002/j.1460-2075.1995.tb07001.x |
| Citation | Swan KA, et al. (1995) Involvement of p21ras distinguishes positive and negative selection in thymocytes. EMBO J 14(2):276-85 |
| abstractText | Small molecular weight GTP binding proteins of the ras family have been implicated in signal transduction from the T cell antigen receptor (TCR). To test the importance of p21ras in the control of thymocyte development, we generated mice expressing a dominant-negative p21ras protein (H-rasN17) in T lineage cells under the control of the lck proximal promoter. Proliferation of thymocytes from lck-H-rasN17 mice in response to TCR stimulation was nearly completely blocked, confirming the importance of p21ras in mediating TCR-derived signals in mature CD4+8- or CD8+4- thymocytes. In contrast, some TCR-derived signals proceeded unimpaired in the CD4+8+ thymocytes of mice expressing dominant-negative p21ras. Analysis of thymocyte development in mice made doubly transgenic for the H-Y-specific TCR and lck-H-rasN17 demonstrated that antigen-specific negative selection occurs normally in the presence of p21H-rasN17. Superantigen-induced negative selection in vivo also proceeded unhindered in H-rasN17 thymocytes. In contrast, positive selection of thymocytes in the H-Y mice was severely compromised by the presence of p21H-rasN17. These observations demonstrate that positive and negative selection, two conceptually antithetical consequences of TCR stimulation, are biochemically distinguishable. |
