| First Author | Lapinski PE | Year | 2011 |
| Journal | J Immunol | Volume | 187 |
| Issue | 1 | Pages | 151-63 |
| PubMed ID | 21646295 | Mgi Jnum | J:176179 |
| Mgi Id | MGI:5288581 | Doi | 10.4049/jimmunol.1100178 |
| Citation | Lapinski PE, et al. (2011) A role for p120 RasGAP in thymocyte positive selection and survival of naive T cells. J Immunol 187(1):151-63 |
| abstractText | Activation of the Ras small GTP-binding protein is necessary for normal T cell development and function. However, it is unknown which Ras GTPase-activating proteins (RasGAPs) inactivate Ras in T cells. We used a T cell-specific RASA1-deficient mouse model to investigate the role of the p120 RasGAP (RASA1) in T cells. Death of CD4(+)CD8(+) double-positive thymocytes was increased in RASA1-deficient mice. Despite this finding, on an MHC class II-restricted TCR transgenic background, evidence was obtained for increased positive selection of thymocytes associated with augmented activation of the Ras-MAPK pathway. In the periphery, RASA1 was found to be dispensable as a regulator of Ras-MAPK activation and T cell functional responses induced by full agonist peptides. However, numbers of naive T cells were substantially reduced in RASA1-deficient mice. Loss of naive T cells in the absence of RASA1 could be attributed in part to impaired responsiveness to the IL-7 prosurvival cytokine. These findings reveal an important role for RASA1 as a regulator of double-positive survival and positive selection in the thymus as well as naive T cell survival in the periphery. |
