Ras-like GTPase (Ral)

Ras-like GTPases (RalA and RalB) are small G proteins belonging to the Ras superfamily that function as critical molecular switches in intracellular signaling (UniProt P11233, P11234). They are primarily activated by Ral guanine nucleotide exchange factors (RalGEFs), which are major downstream effectors of the Ras oncogene (Gentry et al., 2014, Cancer Research). Ral GTPases regulate diverse cellular processes, including receptor endocytosis, exocytosis via the exocyst complex, and actin cytoskeletal remodeling (Neigeborn et al., 2021, Journal of Cell Science). In the context of human disease, Ral signaling is frequently hijacked in various malignancies, particularly those with KRAS mutations, where it drives tumor growth, survival, and metastatic progression (Yan et al., 2014, Nature). Consequently, Ral GTPases have emerged as promising therapeutic targets, with research focusing on small molecules like RBC8 and BQU57 that disrupt their activation or their binding to essential effector proteins (Yan et al., 2014, Nature).

Other names

Ras-related protein Ral-ARas-related protein Ral-BRalARalB

Inhibition of the interaction between Ral GTPases and their downstream effectors (such as the exocyst complex) or inhibition of the activation of Ral by RalGEFs (Yan et al., 2014, Nature; Gentry et al., 2014, Cancer Research).