Disruption of the interaction between mutationally activated Gα_q and Gβγ attenuates aberrant signaling.

ABSTRACT: Heterotrimeric G protein stimulation via G protein-coupled receptors promotes downstream proliferative signaling. Mutations can occur in Gα proteins which prevent GTP hydrolysis; this allows the G proteins to signal independently of G protein-coupled receptors and can result in various cancers, such as uveal melanoma (UM). Most UM cases harbor Q209L, Q209P, or R183C mutations in Gα_q/11 proteins, rendering the proteins constitutively active (CA). Although it is generally thought that active, GTP-bound Gα subunits are dissociated from and signal independently of Gβγ, accumulating evidence indicates that some CA Gα mutants, such as Gα_q/11, retain binding to Gβγ, and this interaction is necessary for signaling. Here, we demonstrate that disrupting the interaction between

SUBMITTER: Aumiller JL 

PROVIDER: S-EPMC9926304 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature