RGS-PX1, a GAP for Gαs and sorting nexin in vesicular trafficking

Heterotrimeric GTP-binding proteins (G proteins) control cellular functions by transducing signals from the outside to the inside of cells. Regulator of G protein signaling (RGS) proteins are key modulators of the amplitude and duration of G protein-mediated signaling through their ability to serve as guanosine triphosphatase-activating proteins (GAPS). We have identified RGS-PX1, a G alpha (s)-specific GAP. The RGS domain of RGS-PX1 specifically interacted with G alpha (s) accelerated its GTP hydrolysis, and attenuated G alpha (s)-mediated signaling. RGS-PX1 also contains a Phox (PX) domain that resembles those in sorting nexin (SNX) proteins. Expression of RGS-PX1 delayed Lysosomal degradation of the EGF receptor. Because of its bifunctional role as both a GAP and a SNX, RGS-PX1 may link heterotrimeric G protein signaling and vesicular trafficking.