Dual phosphorylation of Ric-8A enhances its ability to mediate G protein α subunit folding and to stimulate guanine nucleotide exchange.

ABSTRACT: Resistance to inhibitors of cholinesterase-8A (Ric-8A) and Ric-8B are essential biosynthetic chaperones for heterotrimeric G protein α subunits. We provide evidence for the direct regulation of Ric-8A cellular activity by dual phosphorylation. Using proteomics, Western blotting, and mutational analyses, we determined that Ric-8A was constitutively phosphorylated at five serines and threonines by the protein kinase CK2. Phosphorylation of Ser⁴³⁵ and Thr⁴⁴⁰ in rat Ric-8A (corresponding to Ser⁴³⁶ and Thr⁴⁴¹ in human Ric-8A) was required for high-affinity binding to Gα subunits, efficient stimulation of Gα subunit guanine nucleotide exchange, and mediation of Gα subunit folding. The CK2 consensus sites that contain Ser⁴³⁵ and Thr^440</

SUBMITTER: Papasergi-Scott MM 

PROVIDER: S-EPMC6526509 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature