KRAS (G12C), Isoform A, His-Tag, GppNHp-Loaded Recombinant

RAS is a group of small GTPase proteins encoded by 3 genes (HRAS, NRAS, and KRAS), which play critical roles in regulating cell proliferation. KRAS mutations are responsible for more than 30% of human cancers. The G12C mutation favors the activated (GTP-bound) state of KRAS, amplifying signaling pathways that lead to oncogenesis. Recent studies have led to the discovery of a small molecule called AMG510 (Amgen) that locks KRAS conformation in the GDP-bound (inactive) state, thereby blocking KRAS (G12C) -mediated signaling pathway.The KRAS (Kirsten rat sarcoma virus) gene is subject to alternative splicing, resulting in two isoforms: KRAS-A and KRAS-B. These isoforms differ by amino acids 151,153,165, and 166 and within the hypervariable region (amino acids 167-189) . KRAS-B contains a long polybasic stretch, while KRAS-A has a shorter polybasic region with a palmitoylation site. These differences confer distinct biological characteristics to the two isoforms. When studying a mutant of KRAS, it is important to know which isoform is being studied to make sure that the correct wild-type isoform is used for comparison. The identification of new strategies targeting KRAS G12C will bring large benefits in cancer therapy.