title: A role for p120 RasGAP in thymocyte positive selection and survival of naive T cells.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Philip E
authors.initials: PE
authors.lastname: Lapinski
authors.forename: Yu
authors.initials: Y
authors.lastname: Qiao
authors.forename: Cheong-Hee
authors.initials: CH
authors.lastname: Chang
authors.forename: Philip D
authors.initials: PD
authors.lastname: King
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D020729:p120 GTPase Activating Protein / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020703:ras GTPase-Activating Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: C557248:RASA1 protein, human; D020729:p120 GTPase Activating Protein; D020703:ras GTPase-Activating Proteins