A biochemical and genetic discovery pipeline identifies PLCδ4b as a nonreceptor activator of heterotrimeric G-proteins.

ABSTRACT: Recent evidence has revealed that heterotrimeric G-proteins can be activated by cytoplasmic proteins that share an evolutionarily conserved sequence called the Gα-binding-and-activating (GBA) motif. This mechanism provides an alternative to canonical activation by G-protein-coupled receptors (GPCRs) and plays important roles in cell function, and its dysregulation is linked to diseases such as cancer. Here, we describe a discovery pipeline that uses biochemical and genetic approaches to validate GBA candidates identified by sequence similarity. First, putative GBA motifs discovered in bioinformatics searches were synthesized on peptide arrays and probed in batch for Gα_i3 binding. Then, cDNAs encoding proteins with Gα_i3-binding sequences were expressed in a genetically

SUBMITTER: Maziarz M 

PROVIDER: S-EPMC6222092 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature