Biology Commons^™

Atypical Activation Of The G Protein Gα By The Oncogenic Mutation Q209p, Marcin Maziarz, Anthony Leyme, Arthur Marivin, Alex Luebbers, Prachi P. Patel, Zhe Chen, Stephen R. Sprang, Mikel Garcia-Marcos

Biological Sciences Faculty Publications

The causative role of G protein-coupled receptor (GPCR) pathway mutations in uveal melanoma (UM) has been well-established. Nearly all UMs bear an activating mutation in a GPCR pathway mediated by G proteins of the G family, driving tumor initiation and possibly metastatic progression. Thus, targeting this pathway holds therapeutic promise for managing UM. However, direct targeting of oncogenic Gα mutants, present in ∼90% of UMs, is complicated by the belief that these mutants structurally resemble active Gα WT. This notion is solidly founded on previous studies characterizing Gα mutants in which a conserved catalytic glutamine (Gln-209 in Gα) is replaced …