Son of sevenless homolog 2 (SOS2)

Son of sevenless homolog 2 (SOS2) is a guanine nucleotide exchange factor (GEF) that catalyzes the exchange of GDP for GTP on Ras family proteins, thereby activating Ras and propagating downstream signaling through pathways like PI3K/AKT and MAPK. SOS2 is structurally similar to SOS1 but has unique regulatory features and roles, notably impacting short-term activation of Ras and contributing to cellular proliferation and survival in response to growth factor signals. While SOS1 is considered the dominant GEF in most Ras-related pathologies, SOS2 also plays a critical role, particularly where SOS1 is deficient or absent, and has gained attention as a potential therapeutic target in RAS-driven cancers. Selective small molecule inhibitors against SOS2 have been developed, with quinazoline-based compounds demonstrating high selectivity and affinity for SOS2’s catalytic and interdomain sites. SOS2 is ubiquitously expressed and shares the Ras coupling function with SOS1, but exhibits distinct regulation and stability, impacting disease progression and therapeutic strategies

Other names

Son of sevenless homolog 2SOS2SOS-2NS9guanine nucleotide releasing factorson of sevenless homolog 2, guanine nucleotide releasing factor

Inhibition of guanine nucleotide exchange activity, preventing GDP-to-GTP exchange on Ras; Direct binding to catalytic and interdomain sites of SOS2, blocking its activation of Ras