Ral guanine nucleotide dissociation stimulator-like 2 (RGL2)

Ral guanine nucleotide dissociation stimulator-like 2 (RGL2) is a guanine nucleotide exchange factor (GEF) in the RalGDS family, acting primarily to activate the small GTPase RalA by facilitating GDP-GTP exchange. RGL2 also interacts with Ras and Rap1b and is regulated by phosphorylation via protein kinase A (PKA), which dampens its interaction with H-Ras, implicating it in the fine control of Ras and Ral signaling pathways. RGL2 is associated with processes such as cell migration, apoptosis regulation, signal transduction, and is overexpressed in several disease contexts, including certain cancers (notably pancreatic cancer) and dystrophic cutaneous calcinosis. It functions as a key signaling adaptor, integrating upstream cues from Ras-like proteins to downstream effectors, impacting cell transformation and motility, and is localized at the cytosol and cell’s leading edge. Clinically, no direct drugs target RGL2, but its expression and function make it of interest in oncology and tissue pathophysiology research.

Other names

RAB2LKE1.5HKE1.5RalGDS-like 2RalGDS-like factorRas-associated protein RAB2LGDS-related protein

Not established for drugs (no direct therapeutic inhibitors/agonists identified), but conceptual mechanisms could involve inhibition of GEF activity or modulation of Ras/Ral signaling