Signal Transduct Target Ther. 2021 Nov 15;6(1):386. Nat Cancer. 2023 Aug;4(8):1060-1062.
The KRAS is a member of the rat sarcoma viral oncogene family (RAS), which includes two other isoforms in humans: the Harvey and neuroblastoma rat sarcoma viral oncogenes (HRAS, NRAS). In the resting state, KRAS normally binds with GDP in an inactivated state. When the cells receive the relevant stimuli, such as the interaction of EGF and EGFR, the KRAS-GDP complex appears to have a decreased affinity of KRAS with GDP in the presence of GEFs, and then GDP is replaced by GTP. KRAS-GTP binding acquires an altered conformation in switches I and II of the G domain, and then KRAS is activated and binds to its downstream molecules as a monomer or dimer to mediate a series of signaling cascades. Activated KRAS protein can activate multiple signaling pathways, including the rapidly accelerated fibrosarcoma (RAF)-mitogen-activated protein kinase (MEK)-extracellular regulated protein kinases (ERK) signaling pathway, phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT)—mammalian target of rapamycin (mTOR) signaling pathway, and other signaling pathways, revealing a wide range of KRAS communications with multiple signaling pathways.
2μg (R: reducing condition, N: non-reducing condition).