Presenting Author The Governors Academy Byfield, Massachusetts
The MAPK/ERK signaling pathway is a kinase cascade that promotes cell proliferation. The signaling cascade starts with the binding of epidermal growth factor receptors and progresses to the cell nucleus, resulting in cell growth and division. B-Raf is a signal transduction protein that is crucial in the MAPK/ERK signaling pathway. After interacting with GTP-bound RAS proteins, B-Raf phosphorylates the proteins MEK1 and MEK2, activating molecules that lead to cell proliferation. A mutation in B-Raf contributes significantly to many types of cancers, especially melanoma. Most notably, a single nucleotide mutation resulting in a codon switch, V600E, prompts constitutive activity of B-Raf, which leads to uncontrolled cell division. V600E is the major cause of B-Raf mutation-induced melanoma. Medications like vemurafenib and sorafenib can inhibit the hyperactivity of mutated B-Raf and treat metastatic B-Raf-mutated melanomas. The Governor’s Academy MSOE Center for BioMolecular Modeling MAPS team used 3-D modeling and printing technology to understand how the structures of B-Raf contribute to the phosphorylation of MEK1 and MEK2 and to study the mechanisms of B-Raf inhibitors. Our model highlights features including: the N terminus, the binding site of 14-3-3 protein; the catalytic C terminal region, featuring the kinase domain; and residue 600.
