Ras GTPase-activating protein 2 (RASA2)

Ras GTPase-activating protein 2 (RASA2) is a signaling protein that serves as a negative regulator of the Ras/MAPK pathway by facilitating the conversion of active Ras-GTP to inactive Ras-GDP (UniProt Q15283). It contains several functional domains, including a C2 domain and a PH domain, which allow it to integrate signals from various secondary messengers like inositol phosphates and calcium. In clinical oncology, RASA2 is recognized as a tumor suppressor, and its downregulation or mutation is associated with increased Ras signaling and poor prognosis in cancers such as melanoma (PubMed: 26343582). Beyond its role in cancer cells, RASA2 has emerged as a critical checkpoint in human T cells, where its genetic ablation enhances T-cell receptor signaling and improves the anti-tumor efficacy of adoptive cell therapies (Nature, 2022). Although no small-molecule inhibitors are currently approved for clinical use, RASA2 is a primary target for CRISPR-based engineering in the development of next-generation CAR-T cell therapies.

Other names

GAP1mGAP1(m)RasGAP2GTPase-activating protein of RAS 2

Genetic ablation or inhibition of RASA2 to prevent the inactivation of Ras-GTP, thereby sustaining Ras-mediated signaling pathways to enhance T-cell effector function and persistence.