K-Ras Isoform B (G12V mutant; human, recombinant)

K-Ras is a small GTPase and member of the RAS family of GTPases with roles in apoptosis, as well as cell proliferation, survival, and migration.^1,2 K-Ras is composed of a guanine nucleotide-binding domain containing an active site, an effector binding domain, and an isoform-specific C-terminal hypervariable region (HVR) that differs between K-Ras isoforms A and B due to alternative splicing.^1,3,4 The active site cycles between GDP-bound inactive and GTP-bound active states and is regulated by its associations with GTPase-activating proteins (GAPs) or guanine nucleotide exchange factors (GEFs).^3,5 K-Ras isoform B is ubiquitously expressed and is tethered to the intracellular side of cell membranes via farnesyl lipidation and to negatively charged regions of the membrane via two positively charged polybasic regions in the HVR.^1,6,4 K-Ras^G12V, which contains a glycine-to-valine substitution at position 12, is constitutively active and associated with pancreatic, colon, and lung cancers.⁷ Tumor levels of K-Ras^G12V are negatively correlated with overall survival in patients with colorectal cancer.⁸ Cayman's K-Ras Isoform B (G12V mutant; human, recombinant) protein consists of 184 amino acids, has a calculated molecular weight of 22 kDa, and can be used for enzyme activity assay, inhibitor screening, and inhibitor selectivity profiling applications.

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1. Nussinov, R., Tsai, C.-J., Chakrabarti, M., et al. A new view of Ras isoforms in cancers. Cancer Res. 76(1), 18-23 (2016).

2. Padavano, J., Henkhaus, R.S., Chen, J., et al. Mutant K^-RAS promotes invasion and metastasis in pancreatic cancer through GTPase signaling pathways. Cancer Growth Metastasis 8 (Suppl 1), 95-113 (2015).

3. Hillig, R.C., Sautier, B., Schroeder, J., et al. Discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RAS-SOS1 interaction. Proc. Natl. Acad. Sci. USA 116(7), 2551-2560 (2019).

4. Parker, J.A., and Mattos, C. The K-Ras, N-Ras, and H-Ras isoforms: Unique conformational preferences and implications for targeting oncogenic mutants. Cold Spring Harb. Perspect. Med. 8(8), a031427 (2018).

5. Sermon, B.A., Eccleston, J.F., Skinner, R.H., et al. Mechanism of inhibition by arachidonic acid of the catalytic activity of ras GTPase-activating proteins. The Journal of Biological Chemisty 271(3), 1566-1572 (1996).

6. Salim, A.A., Tan, L., Huang, X.-C., et al. Oligomycins as inhibitors of K-Ras plasma membrane localisation. Org. Biomol. Chem. 14(2), 711-715 (2016).

7. Prior, I.A., Lewis, P.D., and Mattos, C. A comprehensive survey of Ras mutations in cancer. Cancer Res. 72(10), 2457-2467 (2012).

8. Winder, T., Mündlein, A., Rhomberg, S., et al. Different types of K-Ras mutations are conversely associated with overall survival in patients with colorectal cancer. Oncol. Rep. 21(5), 1283-1287 (2009).