PMC

(A). Signal transduction cascade for P-Rex1 activation in neutrophils. Activation of a G-coupled receptor (green) by chemoattractant (CA) stimulates the activation of heterotrimeric G-proteins (orange) and dissociation of Gα from Gβγ. Gβγ directly stimulates PI 3-kinase-γ (PI3Kγ), leading to the production of PIP₃. Both Gβγ and PIP₃ synergize in activating P-Rex1 which catalyzes nucleotide exchange on Rac. Activated Rac then stimulates superoxide activation necessary for pathogen killing and actin polymerization necessary for lamellipodial formation and chemotaxis. (B) Domain structure of P-Rex1. Almost all exchange factors contain a Dbl-homology (DH) domain followed by a pleckstrin homology (PH) domain. P-Rex1 also contains tandem DEP homology domains, tandem PDZ domains, and an apparently enzymatically inactive inositol polyphosphate 4-phosphatase domain.