Abstract
Ras GTPase-activating proteins (RasGAPs) inhibit signal transduction initiated through the Ras small GTP-binding protein. However, which members of the RasGAP family act as negative regulators of T cell responses is not completely understood. In this study, we investigated potential roles for the RasGAPs RASA1 and neurofibromin 1 (NF1) in T cells through the generation and analysis of T cell–specific RASA1 and NF1 double-deficient mice. In contrast to mice lacking either RasGAP alone in T cells, double-deficient mice developed T cell acute lymphoblastic leukemia/lymphoma, which originated at an early point in T cell development and was dependent on activating mutations in the Notch1 gene. These findings highlight RASA1 and NF1 as cotumor suppressors in the T cell lineage.
Footnotes
This work was supported by National Institutes of Health Grants R01 HL096498 and T32 AI007431.
The online version of this article contains supplemental material.
Abbreviations used in this article:
- DKO
- double knockout
- DN
- double-negative
- DP
- double-positive
- ICN
- intracellular Notch
- NF1
- neurofibromin 1
- qPCR
- quantitative PCR
- RASA1
- p120 Ras GTPase-activating protein
- RasGAP
- Ras GTPase-activating protein
- T-ALL
- T cell acute lymphoblastic leukemia/lymphoma.
- Received October 17, 2014.
- Accepted April 28, 2015.
- Copyright © 2015 by The American Association of Immunologists, Inc.
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