The first DEP domain of the RhoGEF P-Rex1 autoinhibits activity and contributes to membrane binding.

ABSTRACT: Phosphatidylinositol (3,4,5)-trisphosphate (PIP₃)-dependent Rac exchanger 1 (P-Rex1) catalyzes the exchange of GDP for GTP on Rac GTPases, thereby triggering changes in the actin cytoskeleton and in transcription. Its overexpression is highly correlated with the metastasis of certain cancers. P-Rex1 recruitment to the plasma membrane and its activity are regulated via interactions with heterotrimeric Gβγ subunits, PIP₃, and protein kinase A (PKA). Deletion analysis has further shown that domains C-terminal to its catalytic Dbl homology (DH) domain confer autoinhibition. Among these, the first dishevelled, Egl-10, and pleckstrin domain (DEP1) remains to be structurally characterized. DEP1 also harbors the primary PKA phosphorylation site, suggesting that an improved un

SUBMITTER: Ravala SK 

PROVIDER: S-EPMC7476721 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature