| First Author | Pérez de Castro I | Year | 2003 |
| Journal | Cancer Res | Volume | 63 |
| Issue | 7 | Pages | 1615-22 |
| PubMed ID | 12670913 | Mgi Jnum | J:82648 |
| Mgi Id | MGI:2654312 | Citation | de Castro IP, et al. (2003) Mice deficient for N-ras: impaired antiviral immune response and T-cell function. Cancer Res 63(7):1615-22 |
| abstractText | Ras proteins have a key role in the regulation of several cellular functions, and are involved in a significant percentage of human tumors. However, the specific functions of the different Ras isoforms are poorly understood. In this work, we show for the first time a specific role for N-ras in T-cell function and development. Mice defective for N-ras have low numbers of CD8 single positive thymocytes and decreased thymocyte proliferation in vitro. In Ras signaling and activation assays, KO-N-ras thymocytes showed a defective response to T-cell activation. In turn, these deficiencies resulted in a significant reduction in the production of interleukin 2 on thymocyte activation. We have also detected in vivo the functional consequences of N-ras deficiency. KO-N-ras mice showed an increased sensitivity to influenza infection, especially when low doses of virus were used. Finally, we have detected an abnormal activation pattern of downstream Ras molecules in T-cell receptor-activated KO-N-ras thymocytes that is consistent with the defective T-cell function found in these animals. All of the results derived from this work constitute a significant contribution to the knowledge of N-ras-specific functions. |
