Interaction kinetics between p115-RhoGEF and Gα₁₃ are determined by unique molecular interactions affecting agonist sensitivity.

ABSTRACT: The three RH-RhoGEFs (Guanine nucleotide exchange factors) p115-RhoGEF, LARG (leukemia-associated RhoGEF) and PDZ-RhoGEF link G-protein coupled receptors (GPCRs) with RhoA signaling through activation of Gα_12/13. In order to find functional differences in signaling between the different RH-RhoGEFs we examined their interaction with Gα₁₃ in high spatial and temporal resolution, utilizing a FRET-based single cell assay. We found that p115-RhoGEF interacts significantly shorter with Gα₁₃ than LARG and PDZ-RhoGEF, while narrowing the structural basis for these differences down to a single amino acid in the rgRGS domain of p115-RhoGEF. The mutation of this amino acid led to an increased interaction time with Gα₁₃ and an enhanced agonist sensitivity, c

SUBMITTER: Redlin F 

PROVIDER: S-EPMC9700851 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature