RGS-PX1, a GAP for GalphaS 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 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.
Zheng
B
B
Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093-0651, USA.
Ma
Y C
YC
Ostrom
R S
RS
Lavoie
C
C
Gill
G N
GN
Insel
P A
PA
Huang
X Y
XY
Farquhar
M G
MG
D058666:Adrenergic beta-2 Receptor Agonists; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002417:Cattle; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D011992:Endosomes / Q000737:chemistry / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000737:chemistry / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D020710:RGS Proteins / Q000737:chemistry / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction; D058305:Sorting Nexins; D013379:Substrate Specificity; D033921:Vesicular Transport Proteins
D058666:Adrenergic beta-2 Receptor Agonists; D002352:Carrier Proteins; D020690:GTPase-Activating Proteins; D020710:RGS Proteins; D018343:Receptors, Adrenergic, beta-2; C442319:SNX13 protein, human; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins; D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases; D019205:GTP-Binding Protein alpha Subunits, Gs