KRAS 2B Human

The Kirsten Rat Sarcoma Viral Oncogene (KRAS) is a gene that encodes a protein known as K-Ras, which is part of the small GTPase superfamily. This gene plays a crucial role in cell signaling pathways that control cell growth, differentiation, and survival. The KRAS gene is a member of the RAS gene family, which also includes HRAS and NRAS .

The KRAS gene was first identified as a viral oncogene in the Kirsten Rat Sarcoma virus, hence the name . The oncogene identified was derived from a cellular genome, so when found in a cellular genome, KRAS is referred to as a proto-oncogene .

The KRAS gene produces two main protein isoforms through alternative splicing: K-Ras4A and K-Ras4B . These isoforms differ in their C-terminal regions, which affects their localization and function within the cell. Isoform 2B, specifically, is one of these variants that has been studied for its role in various cellular processes and malignancies .

K-Ras acts as a molecular switch, cycling between an active GTP-bound state and an inactive GDP-bound state . When active, K-Ras recruits and activates several downstream signaling pathways, including the MAPK/ERK pathway, which is essential for cell proliferation and differentiation . This protein is tethered to cell membranes due to the presence of an isoprene group on its C-terminus .

Mutations in the KRAS gene are among the most common oncogenic alterations found in human cancers . These mutations often result in a constitutively active K-Ras protein that continuously signals for cell growth and division, leading to uncontrolled cell proliferation. KRAS mutations are frequently observed in lung adenocarcinoma, colorectal carcinoma, pancreatic ductal adenocarcinoma, and other malignancies .

Despite its critical role in cancer, targeting KRAS for therapeutic intervention has been challenging . The protein’s structure makes it difficult to develop inhibitors that can effectively block its activity. However, recent advances in drug development have led to the discovery of some promising inhibitors that are currently being tested in clinical trials .