Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 294 (5548): 1939-1942

Copyright © 2001 by the American Association for the Advancement of Science

RGS-PX1, a GAP for Galpha s and Sorting Nexin in Vesicular Trafficking

Bin Zheng,12* Yong-Chao Ma,5* Rennolds S. Ostrom,3 Christine Lavoie,1 Gordon N. Gill,41 Paul A. Insel,3 Xin-Yun Huang,5 Marilyn G. Farquhar12dagger

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.

1 Department of Cellular and Molecular Medicine,
2 Department of Pathology,
3 Department of Pharmacology,
4 Department of Medicine, University of California San Diego, La Jolla, CA 92093-0651, USA.
5 Department of Physiology, Weill Medical College of Cornell University, New York, NY 10021, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: mfarquhar{at}

Regulator of G-protein Signaling-21 (RGS21) Is an Inhibitor of Bitter Gustatory Signaling Found in Lingual and Airway Epithelia.
S. P. Cohen, B. K. Buckley, M. Kosloff, A. L. Garland, D. E. Bosch, G. Cheng Jr, H. Radhakrishna, M. D. Brown, F. S. Willard, V. Y. Arshavsky, et al. (2012)
J. Biol. Chem. 287, 41706-41719
   Abstract »    Full Text »    PDF »
Extra-long G{alpha}s Variant XL{alpha}s Protein Escapes Activation-induced Subcellular Redistribution and Is Able to Provide Sustained Signaling.
Z. Liu, S. Turan, V. L. Wehbi, J.-P. Vilardaga, and M. Bastepe (2011)
J. Biol. Chem. 286, 38558-38569
   Abstract »    Full Text »    PDF »
Regulators of G-Protein Signaling in the Heart and Their Potential as Therapeutic Targets.
P. Zhang and U. Mende (2011)
Circ. Res. 109, 320-333
   Abstract »    Full Text »    PDF »
Phox homology band 4.1/ezrin/radixin/moesin-like proteins function as molecular scaffolds that interact with cargo receptors and Ras GTPases.
R. Ghai, M. Mobli, S. J. Norwood, A. Bugarcic, R. D. Teasdale, G. F. King, and B. M. Collins (2011)
PNAS 108, 7763-7768
   Abstract »    Full Text »    PDF »
Tumor suppressor p27Kip1 undergoes endolysosomal degradation through its interaction with sorting nexin 6.
J. J. Fuster, J. M. Gonzalez, M. D. Edo, R. Viana, P. Boya, J. Cervera, M. Verges, J. Rivera, and V. Andres (2010)
FASEB J 24, 2998-3009
   Abstract »    Full Text »    PDF »
Ric-8B Stabilizes the {alpha} Subunit of Stimulatory G Protein by Inhibiting Its Ubiquitination.
Y. Nagai, A. Nishimura, K. Tago, N. Mizuno, and H. Itoh (2010)
J. Biol. Chem. 285, 11114-11120
   Abstract »    Full Text »    PDF »
Characterization of PXK as a Protein Involved in Epidermal Growth Factor Receptor Trafficking.
H. Takeuchi, T. Takeuchi, J. Gao, L. C. Cantley, and M. Hirata (2010)
Mol. Cell. Biol. 30, 1689-1702
   Abstract »    Full Text »    PDF »
Suppression of prostaglandin E2-induced MUC5AC overproduction by RGS4 in the airway.
K. S. Song, Y. H. Choi, J.-M. Kim, H. Lee, T.-J. Lee, and J.-H. Yoon (2009)
Am J Physiol Lung Cell Mol Physiol 296, L684-L692
   Abstract »    Full Text »    PDF »
Function and dysfunction of the PI system in membrane trafficking.
M. Vicinanza, G. D'Angelo, A. Di Campli, and M. A. De Matteis (2008)
EMBO J. 27, 2457-2470
   Abstract »    Full Text »    PDF »
Large-scale quantitative LC-MS/MS analysis of detergent-resistant membrane proteins from rat renal collecting duct.
M.-J. Yu, T. Pisitkun, G. Wang, J. F. Aranda, P. A. Gonzales, D. Tchapyjnikov, R.-F. Shen, M. A. Alonso, and M. A. Knepper (2008)
Am J Physiol Cell Physiol 295, C661-C678
   Abstract »    Full Text »    PDF »
Physiological functions of the imprinted Gnas locus and its protein variants G{alpha}s and XL{alpha}s in human and mouse.
A. Plagge, G. Kelsey, and E. L Germain-Lee (2008)
J. Endocrinol. 196, 193-214
   Abstract »    Full Text »    PDF »
Renal Albumin Excretion: Twin Studies Identify Influences of Heredity, Environment, and Adrenergic Pathway Polymorphism.
F. Rao, J. Wessel, G. Wen, L. Zhang, B. K. Rana, B. P. Kennedy, T. A. Greenwood, R. M. Salem, Y. Chen, S. Khandrika, et al. (2007)
Hypertension 49, 1015-1031
   Abstract »    Full Text »    PDF »
Rgs1 regulates multiple G{alpha} subunits in Magnaporthe pathogenesis, asexual growth and thigmotropism.
H. Liu, A. Suresh, F. S. Willard, D. P. Siderovski, S. Lu, and N. I. Naqvi (2007)
EMBO J. 26, 690-700
   Abstract »    Full Text »    PDF »
Molecular Mechanism of Membrane Docking by the Vam7p PX Domain.
S. A. Lee, J. Kovacs, R. V. Stahelin, M. L. Cheever, M. Overduin, T. G. Setty, C. G. Burd, W. Cho, and T. G. Kutateladze (2006)
J. Biol. Chem. 281, 37091-37101
   Abstract »    Full Text »    PDF »
Essential role of RGS-PX1/sorting nexin 13 in mouse development and regulation of endocytosis dynamics.
B. Zheng, T. Tang, N. Tang, K. Kudlicka, K. Ohtsubo, P. Ma, J. D. Marth, M. G. Farquhar, and E. Lehtonen (2006)
PNAS 103, 16776-16781
   Abstract »    Full Text »    PDF »
GS Activation Is Time-limiting in Initiating Receptor-mediated Signaling.
P. Hein, F. Rochais, C. Hoffmann, S. Dorsch, V. O. Nikolaev, S. Engelhardt, C. H. Berlot, M. J. Lohse, and M. Bunemann (2006)
J. Biol. Chem. 281, 33345-33351
   Abstract »    Full Text »    PDF »
Furin-, ADAM 10-, and {gamma}-Secretase-Mediated Cleavage of a Receptor Tyrosine Phosphatase and Regulation of {beta}-Catenin's Transcriptional Activity.
L. Anders, P. Mertins, S. Lammich, M. Murgia, D. Hartmann, P. Saftig, C. Haass, and A. Ullrich (2006)
Mol. Cell. Biol. 26, 3917-3934
   Abstract »    Full Text »    PDF »
Genome-Scale Analysis Reveals Sst2 as the Principal Regulator of Mating Pheromone Signaling in the Yeast Saccharomyces cerevisiae.
S. A. Chasse, P. Flanary, S. C. Parnell, N. Hao, J. Y. Cha, D. P. Siderovski, and H. G. Dohlman (2006)
Eukaryot. Cell 5, 330-346
   Abstract »    Full Text »    PDF »
Can a GDP-Liganded G-Protein Be Active?.
T. Wieland and M. C. Michel (2005)
Mol. Pharmacol. 68, 559-562
   Abstract »    Full Text »    PDF »
Identification and Characterization of GIV, a Novel G{alpha}i/s -interacting Protein Found on COPI, Endoplasmic Reticulum-Golgi Transport Vesicles.
H. Le-Niculescu, I. Niesman, T. Fischer, L. DeVries, and M. G. Farquhar (2005)
J. Biol. Chem. 280, 22012-22020
   Abstract »    Full Text »    PDF »
Multi-Tasking RGS Proteins in the Heart: The Next Therapeutic Target?.
E. L. Riddle, R. A. Schwartzman, M. Bond, and P. A. Insel (2005)
Circ. Res. 96, 401-411
   Abstract »    Full Text »    PDF »
RGS14 Is a Centrosomal and Nuclear Cytoplasmic Shuttling Protein That Traffics to Promyelocytic Leukemia Nuclear Bodies Following Heat Shock.
H. Cho, D.-U. Kim, and J. H. Kehrl (2005)
J. Biol. Chem. 280, 805-814
   Abstract »    Full Text »    PDF »
Regulation of Epidermal Growth Factor Receptor Degradation by Heterotrimeric G{alpha}s Protein.
B. Zheng, C. Lavoie, T.-D. Tang, P. Ma, T. Meerloo, A. Beas, and M. G. Farquhar (2004)
Mol. Biol. Cell 15, 5538-5550
   Abstract »    Full Text »    PDF »
A Retinal-Specific Regulator of G-Protein Signaling Interacts with G{alpha}o and Accelerates an Expressed Metabotropic Glutamate Receptor 6 Cascade.
A. Dhingra, E. Faurobert, N. Dascal, P. Sterling, and N. Vardi (2004)
J. Neurosci. 24, 5684-5693
   Abstract »    Full Text »    PDF »
YXXM Motifs in the PDGF-{beta} Receptor Serve Dual Roles as Phosphoinositide 3-Kinase Binding Motifs and Tyrosine-based Endocytic Sorting Signals.
H. Wu, D. A. Windmiller, L. Wang, and J. M. Backer (2003)
J. Biol. Chem. 278, 40425-40428
   Abstract »    Full Text »    PDF »
Evidence for a Role of SNX16 in Regulating Traffic between the Early and Later Endosomal Compartments.
B. J. Hanson and W. Hong (2003)
J. Biol. Chem. 278, 34617-34630
   Abstract »    Full Text »    PDF »
Recruitment of RGS2 and RGS4 to the Plasma Membrane by G Proteins and Receptors Reflects Functional Interactions.
A. A. Roy, K. E. Lemberg, and P. Chidiac (2003)
Mol. Pharmacol. 64, 587-593
   Abstract »    Full Text »    PDF »
Mild Heat and Proteotoxic Stress Promote Unique Subcellular Trafficking and Nucleolar Accumulation of RGS6 and Other RGS Proteins: ROLE OF THE RGS DOMAIN IN STRESS-INDUCED TRAFFICKING OF RGS PROTEINS.
T. K. Chatterjee and R. A. Fisher (2003)
J. Biol. Chem. 278, 30272-30282
   Abstract »    Full Text »    PDF »
Essential Ca2+-independent Role of the Group IVA Cytosolic Phospholipase A2 C2 Domain for Interfacial Activity.
D. A. Six and E. A. Dennis (2003)
J. Biol. Chem. 278, 23842-23850
   Abstract »    Full Text »    PDF »
Enterophilin-1, a New Partner of Sorting Nexin 1, Decreases Cell Surface Epidermal Growth Factor Receptor.
V. Pons, F. Hullin-Matsuda, M. Nauze, R. Barbaras, C. Peres, X. Collet, B. Perret, H. Chap, and A. Gassama-Diagne (2003)
J. Biol. Chem. 278, 21155-21161
   Abstract »    Full Text »    PDF »
A. Hiol, P. C. Davey, J. L. Osterhout, A. A. Waheed, E. R. Fischer, C.-K. Chen, G. Milligan, K. M. Druey, and T. L. Z. Jones (2003)
J. Biol. Chem. 278, 19301-19308
   Abstract »    Full Text »    PDF »
Identification of RGS2 and Type V Adenylyl Cyclase Interaction Sites.
S. Salim, S. Sinnarajah, J. H. Kehrl, and C. W. Dessauer (2003)
J. Biol. Chem. 278, 15842-15849
   Abstract »    Full Text »    PDF »
Trafficking Patterns of beta -Arrestin and G Protein-coupled Receptors Determined by the Kinetics of beta -Arrestin Deubiquitination.
S. K. Shenoy and R. J. Lefkowitz (2003)
J. Biol. Chem. 278, 14498-14506
   Abstract »    Full Text »    PDF »
Distinct Phosphoinositide 3-Kinases Mediate Mast Cell Degranulation in Response to G-protein-coupled VersusFc{varepsilon}RI Receptors.
D. A. Windmiller and J. M. Backer (2003)
J. Biol. Chem. 278, 11874-11878
   Abstract »    Full Text »    PDF »
Regulators of G-protein Signaling (RGS) 4, Insertion into Model Membranes and Inhibition of Activity by Phosphatidic Acid.
Y.-S. Ouyang, Y. Tu, S. A. Barker, and F. Yang (2003)
J. Biol. Chem. 278, 11115-11122
   Abstract »    Full Text »    PDF »
RGS6, RGS7, RGS9, and RGS11 Stimulate GTPase Activity of Gi Family G-proteins with Differential Selectivity and Maximal Activity.
S. B. Hooks, G. L. Waldo, J. Corbitt, E. T. Bodor, A. M. Krumins, and T. K. Harden (2003)
J. Biol. Chem. 278, 10087-10093
   Abstract »    Full Text »    PDF »
GDE1/MIR16 is a glycerophosphoinositol phosphodiesterase regulated by stimulation of G protein-coupled receptors.
B. Zheng, C. P. Berrie, D. Corda, and M. G. Farquhar (2003)
PNAS 100, 1745-1750
   Abstract »    Full Text »    PDF »
R. Sterne-Marr, J. J. G. Tesmer, P. W. Day, R. P. Stracquatanio, J.-A. E. Cilente, K. E. O'Connor, A. N. Pronin, J. L. Benovic, and P. B. Wedegaertner (2003)
J. Biol. Chem. 278, 6050-6058
   Abstract »    Full Text »    PDF »
Systemic effects of chronic obstructive pulmonary disease.
A.G.N. Agusti, A. Noguera, J. Sauleda, E. Sala, J. Pons, and X. Busquets (2003)
Eur. Respir. J. 21, 347-360
   Abstract »    Full Text »    PDF »
Cellular Regulation of RGS Proteins: Modulators and Integrators of G Protein Signaling.
S. Hollinger and J. R. Hepler (2002)
Pharmacol. Rev. 54, 527-559
   Abstract »    Full Text »    PDF »
RGS13 Regulates Germinal Center B Lymphocytes Responsiveness to CXC Chemokine Ligand (CXCL)12 and CXCL13.
G.-X. Shi, K. Harrison, G. L. Wilson, C. Moratz, and J. H. Kehrl (2002)
J. Immunol. 169, 2507-2515
   Abstract »    Full Text »    PDF »
Focus on "Targeted expression of activated Q227L Galpha s in vivo".
S. F. Steinberg (2002)
Am J Physiol Cell Physiol 283, C383-C385
   Full Text »    PDF »
Receptor-selective Effects of Endogenous RGS3 and RGS5 to Regulate Mitogen-activated Protein Kinase Activation in Rat Vascular Smooth Muscle Cells.
Q. Wang, M. Liu, B. Mullah, D. P. Siderovski, and R. R. Neubig (2002)
J. Biol. Chem. 277, 24949-24958
   Abstract »    Full Text »    PDF »
Regulation of Stress Response Signaling by the N-terminal Dishevelled/EGL-10/Pleckstrin Domain of Sst2, a Regulator of G Protein Signaling in Saccharomyces cerevisiae.
S. A. Burchett, P. Flanary, C. Aston, L. Jiang, K. H. Young, P. Uetz, S. Fields, and H. G. Dohlman (2002)
J. Biol. Chem. 277, 22156-22167
   Abstract »    Full Text »    PDF »
Endosomal localization and function of sorting nexin 1.
Q. Zhong, C. S. Lazar, H. Tronchere, T. Sato, T. Meerloo, M. Yeo, Z. Songyang, S. D. Emr, and G. N. Gill (2002)
PNAS 99, 6767-6772
   Abstract »    Full Text »    PDF »
Functional Characterization of the G Protein Regulator RGS13.
E. N. Johnson and K. M. Druey (2002)
J. Biol. Chem. 277, 16768-16774
   Abstract »    Full Text »    PDF »
Heterotrimeric and Unconventional GTP Binding Proteins in Plant Cell Signaling.
S. M. Assmann (2002)
PLANT CELL 14, S355-S373
   Full Text »    PDF »
Activator of G-protein Signaling 1 Blocks GIRK Channel Activation by a G-protein-coupled Receptor. APPARENT DISRUPTION OF RECEPTOR SIGNALING COMPLEXES.
A. Takesono, M. W. Nowak, M. Cismowski, E. Duzic, and S. M. Lanier (2002)
J. Biol. Chem. 277, 13827-13830
   Abstract »    Full Text »    PDF »
The PX domain: a new phosphoinositide-binding module.
C. D. Ellson, S. Andrews, L. R. Stephens, and P. T. Hawkins (2002)
J. Cell Sci. 115, 1099-1105
   Abstract »    Full Text »    PDF »
SIGNAL TRANSDUCTION: A New Thread in an Intricate Web.
M. v. Zastrow and K. Mostov (2001)
Science 294, 1845-1847
   Full Text »    PDF »
Location, Location, Location: Membrane Targeting Directed by PX Domains.
T. K. Sato, M. Overduin, and S. D. Emr (2001)
Science 294, 1881-1885
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882