RGS-PX1, a GAP for G[α.sub.s] and sorting nexin in vesicular trafficking. (Reports)

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 [Gα.sub.s]-specific GAP. The RGS domain of RGS-PX1 specifically interacted with [Gα.sub.s], accelerated its GTP hydrolysis, and attenuated [Gα.sub.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.
Heterotrimeric G proteins relay extracellular signals initiated by hormones, neurotransmitters, chemokines, and sensory stimuli through G protein-coupled receptors to intracellular effectors and trigger a variety of physiological responses (1, 2). [...]