Atypical activation of the G protein Gα_q by the oncogenic mutation Q209P.

ABSTRACT: 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_q/11 family, driving tumor initiation and possibly metastatic progression. Thus, targeting this pathway holds therapeutic promise for managing UM. However, direct targeting of oncogenic Gα_q/11 mutants, present in ∼90% of UMs, is complicated by the belief that these mutants structurally resemble active Gα_q/11 WT. This notion is solidly founded on previous studies characterizing Gα mutants in which a conserved catalytic glutamine (Gln-209 in Gα_q) is replaced by leucine, which leads to GTPase function deficiency and constitutive activati

SUBMITTER: Maziarz M 

PROVIDER: S-EPMC6314142 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature