![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 58, Issue 4, 719-728, October 2000
and
Gq and a Potent Inhibitor of Signaling by
GTPase-Deficient Forms of Gq and G11
B Cell Molecular Biology Section, Laboratory Immunoregulation,
National Institutes of Health, Bethesda, Maryland (A.S., S.S., C.-S.S.,
H.H.K.); and the University of Texas, Southwestern Medical
Center, Department of Pharmacology, Dallas, Texas (C.W.D., P.C.)
Many Regulators of G protein
Signaling (RGS) proteins accelerate the intrinsic GTPase
activity of Gi
and Gq-subunits [i.e.,
behave as GTPase-activating proteins (GAPs)] and several act as
Gq-effector antagonists. RGS3, a structurally distinct RGS member with a unique N-terminal domain and a C-terminal RGS domain,
and an N-terminally truncated version of RGS3 (RGS3CT) both stimulated
the GTPase activity of Gi (except Gz) and
Gq but not that of Gs or
G12. RGS3 and RGS3CT had Gq GAP activity
similar to that of RGS4. RGS3 impaired signaling through
Gq-linked receptors, although RGS3CT invariably inhibited
better than did full-length RGS3. RGS3 potently inhibited GqQ209L- and
G11Q209L-mediated activation of a
cAMP-response element-binding protein reporter gene and
GqQ209L induced inositol phosphate production,
suggesting that RGS3 efficiently blocks Gq from
activating its downstream effector phospholipase C-
. Whereas
RGS2 and to a lesser extent RGS10 also inhibited signaling by these
GTPase-deficient G proteins, other RGS proteins including RGS4 did not.
Mutation of residues in RGS3 similar to those required for RGS4
Gi GAP activity, as well as several residues N terminal
to its RGS domain impaired RGS3 function. A greater percentage of
RGS3CT localized at the cell membrane than the full-length version,
potentially explaining why RGS3CT blocked signaling better than did
full-length RGS3. Thus, RGS3 can impair Gi- (but not Gz-) and
Gq-mediated signaling in hematopoietic and other cell types by acting
as a GAP for Gi and Gq subfamily members
and as a potent Gq subfamily effector antagonist.
This article has been cited by other articles:
|
|
 |
|
  U. Meza, A. Thapliyal, R. A. Bannister, and B. A. Adams Neurokinin 1 Receptors Trigger Overlapping Stimulation and Inhibition of CaV2.3 (R-Type) Calcium Channels Mol. Pharmacol., January 1, 2007; 71(1): 284 - 293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Toro-Castillo, A. Thapliyal, H. Gonzalez-Ochoa, B. A. Adams, and U. Meza Muscarinic modulation of Cav2.3 (R-type) calcium channels is antagonized by RGS3 and RGS3T Am J Physiol Cell Physiol, January 1, 2007; 292(1): C573 - C580. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Jaen and C. A. Doupnik RGS3 and RGS4 Differentially Associate with G Protein-coupled Receptor-Kir3 Channel Signaling Complexes Revealing Two Modes of RGS Modulation: PRECOUPLING AND COLLISION COUPLING J. Biol. Chem., November 10, 2006; 281(45): 34549 - 34560. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Roy, C. Nunn, H. Ming, M.-X. Zou, J. Penninger, L. A. Kirshenbaum, S. J. Dixon, and P. Chidiac Up-regulation of Endogenous RGS2 Mediates Cross-desensitization between Gs and Gq Signaling in Osteoblasts J. Biol. Chem., October 27, 2006; 281(43): 32684 - 32693. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Profirovic, M. Gorovoy, J. Niu, S. Pavlovic, and T. Voyno-Yasenetskaya{paragraph} A Novel Mechanism of G Protein-dependent Phosphorylation of Vasodilator-stimulated Phosphoprotein J. Biol. Chem., September 23, 2005; 280(38): 32866 - 32876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Tovey and G. B. Willars Single-Cell Imaging of Intracellular Ca2+ and Phospholipase C Activity Reveals That RGS 2, 3, and 4 Differentially Regulate Signaling via the G{alpha}q/11-Linked Muscarinic M3 Receptor Mol. Pharmacol., December 1, 2004; 66(6): 1453 - 1464. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Le Stunff, A. Mikami, P. Giussani, J. P Hobson, P. S. Jolly, S. Milstien, and S. Spiegel Role of Sphingosine-1-phosphate Phosphatase 1 in Epidermal Growth Factor-induced Chemotaxis J. Biol. Chem., August 13, 2004; 279(33): 34290 - 34297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.-X. Shi, K. Harrison, S.-B. Han, C. Moratz, and J. H. Kehrl Toll-Like Receptor Signaling Alters the Expression of Regulator of G Protein Signaling Proteins in Dendritic Cells: Implications for G Protein-Coupled Receptor Signaling J. Immunol., May 1, 2004; 172(9): 5175 - 5184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Anger, W. Zhang, and U. Mende Differential Contribution of GTPase Activation and Effector Antagonism to the Inhibitory Effect of RGS Proteins on Gq-mediated Signaling in Vivo J. Biol. Chem., February 6, 2004; 279(6): 3906 - 3915. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Olivera, H. M. Rosenfeldt, M. Bektas, F. Wang, I. Ishii, J. Chun, S. Milstien, and S. Spiegel Sphingosine Kinase Type 1 Induces G12/13-mediated Stress Fiber Formation, yet Promotes Growth and Survival Independent of G Protein-coupled Receptors J. Biol. Chem., November 21, 2003; 278(47): 46452 - 46460. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Lippert, D. L. Yowe, J.-A. Gonzalo, J. P. Justice, J. M. Webster, E. R. Fedyk, M. Hodge, C. Miller, J.-C. Gutierrez-Ramos, F. Borrego, et al. Role of Regulator of G Protein Signaling 16 in Inflammation- Induced T Lymphocyte Migration and Activation J. Immunol., August 1, 2003; 171(3): 1542 - 1555. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Tosetti, N. Pathak, M. H. Jacob, and K. Dunlap RGS3 mediates a calcium-dependent termination of G protein signaling in sensory neurons PNAS, June 10, 2003; 100(12): 7337 - 7342. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Salim, S. Sinnarajah, J. H. Kehrl, and C. W. Dessauer Identification of RGS2 and Type V Adenylyl Cyclase Interaction Sites J. Biol. Chem., April 25, 2003; 278(18): 15842 - 15849. [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 G Protein-coupled Receptor Kinase 2/Galpha q/11 Interaction. A NOVEL SURFACE ON A REGULATOR OF G PROTEIN SIGNALING HOMOLOGY DOMAIN FOR BINDING Galpha SUBUNITS J. Biol. Chem., February 14, 2003; 278(8): 6050 - 6058. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wang, G. Ho, J. J. Zhang, B. Nieuwenhuijsen, W. Edris, P. K. Chanda, and K. H. Young Regulator of G Protein Signaling Z1 (RGSZ1) Interacts with Galpha i Subunits and Regulates Galpha i-mediated Cell Signaling J. Biol. Chem., December 6, 2002; 277(50): 48325 - 48332. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Bannister, K. Melliti, and B. A. Adams Reconstituted Slow Muscarinic Inhibition of Neuronal (CaV1.2c) L-Type Ca2+ Channels Biophys. J., December 1, 2002; 83(6): 3256 - 3267. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Cladman and P. Chidiac Characterization and Comparison of RGS2 and RGS4 as GTPase-Activating Proteins for m2 Muscarinic Receptor-Stimulated Gi Mol. Pharmacol., September 1, 2002; 62(3): 654 - 659. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Wang, M. Liu, B. Mullah, D. P. Siderovski, and R. R. Neubig Receptor-selective Effects of Endogenous RGS3 and RGS5 to Regulate Mitogen-activated Protein Kinase Activation in Rat Vascular Smooth Muscle Cells J. Biol. Chem., July 5, 2002; 277(28): 24949 - 24958. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Castro-Fernandez, J. A. Janovick, S. P. Brothers, R. A. Fisher, T. H. Ji, and P. M. Conn Regulation of RGS3 and RGS10 Palmitoylation by GnRH Endocrinology, April 1, 2002; 143(4): 1310 - 1317. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nagahama, S. Usui, T. Shinohara, T. Yamaguchi, K. Tani, and M. Tagaya Inactivation of G{alpha}z causes disassembly of the Golgi apparatus J. Cell Sci., January 12, 2002; 115(23): 4483 - 4493. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. J. Watts, R. Taussig, R. L. Neve, and K. A. Neve Dopamine D2 Receptor-Induced Heterologous Sensitization of Adenylyl Cyclase Requires Galpha s: Characterization of Galpha s-Insensitive Mutants of Adenylyl Cyclase V Mol. Pharmacol., December 1, 2001; 60(6): 1168 - 1172. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-S. Shi, S. B. Lee, S. Sinnarajah, C. W. Dessauer, S. G. Rhee, and J. H. Kehrl Regulator of G-protein Signaling 3 (RGS3) Inhibits Gbeta 1gamma 2-induced Inositol Phosphate Production, Mitogen-activated Protein Kinase Activation, and Akt Activation J. Biol. Chem., June 22, 2001; 276(26): 24293 - 24300. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
