Zheng B, Ma Y C, Ostrom R S, Lavoie C, Gill G N, Insel P A, Huang X Y, Farquhar M G
Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093-0651, USA.
Science. 2001 Nov 30;294(5548):1939-42. doi: 10.1126/science.1064757.
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 Galpha(s)-specific GAP. The RGS domain of RGS-PX1 specifically interacted with Galpha(s), accelerated its GTP hydrolysis, and attenuated Galpha(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.
异源三聚体GTP结合蛋白（G蛋白）通过将信号从细胞外传递到细胞内来控制细胞功能。G蛋白信号调节剂（RGS）蛋白是G蛋白介导信号传导幅度和持续时间的关键调节因子，因为它们能够作为鸟苷三磷酸酶激活蛋白（GAP）发挥作用。我们鉴定出了RGS-PX1，一种特异性作用于Gαs的GAP。RGS-PX1的RGS结构域与Gαs特异性相互作用，加速其GTP水解，并减弱Gαs介导的信号传导。RGS-PX1还包含一个与分选连接蛋白（SNX）蛋白中的结构域类似的Phox（PX）结构域。RGS-PX1的表达延迟了表皮生长因子受体的溶酶体降解。由于RGS-PX1兼具GAP和SNX的双重功能，它可能将异源三聚体G蛋白信号传导与囊泡运输联系起来。
