Ras-related protein Ral-A (RalA) (RalA)

Ras-related protein Ral-A (RalA) is a small GTPase belonging to the Ras superfamily that acts as a molecular switch in various signaling pathways [1]. It cycles between an inactive GDP-bound state and an active GTP-bound state, regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) [1, 3]. RalA plays a critical role in regulating vesicle trafficking, exocytosis, and actin cytoskeleton remodeling, particularly through its interactions with the exocyst complex [3, 4]. In oncology, RalA is frequently overactivated downstream of oncogenic Ras, contributing to tumor growth, metastasis, and survival in cancers such as pancreatic, lung, and colorectal carcinomas [3]. Therapeutic strategies often focus on stabilizing the inactive RalA-GDP conformation or blocking its interaction with effectors like Sec5 and Exo84 [2]. Small molecule inhibitors such as RBC8 and BQU57 have been developed to bind specifically to a pocket on the GDP-bound form, effectively preventing its transition to the active state and inhibiting tumor progression in preclinical models [2, 4].

Other names

Ras-like protein Av-ral simian leukemia viral oncogene homolog ARAL

Allosteric inhibition of the GDP-bound state to prevent nucleotide exchange and effector binding