The extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway is crucial for cell proliferation. Specific types of cancers, including malignant melanoma, contain activating mutations in the BRAF kinase, which is an upstream regulator of ERK1/2, leading to uncontrolled proliferation. One docking site in ERK1/2 that has been targeted controls the activation of oncogenic transcription factors. Compounds identified to target this substrate docking site were found to covalently interact with a specific cysteine.1,2 To evaluate the role of this cysteine in ERK1/2 signaling, CRISPR CAS9 was used to generate isogenic cell lines with cysteine mutations in both ERK1 and ERK2. The proposed studies investigate the effects the ERK1/2 cysteine mutations have on A375 melanoma cells regarding cell signaling and proliferation