scholarly journals The Regulator of G Protein Signaling RGS4 Selectively Enhances α2A-Adreoreceptor Stimulation of the GTPase Activity of Go1α and Gi2α

2000 ◽  
Vol 275 (31) ◽  
pp. 23693-23699 ◽  
Author(s):  
Antonella Cavalli ◽  
Kirk M. Druey ◽  
Graeme Milligan
Keyword(s):  
G Protein ◽  
G Protein Signaling ◽  
Gtpase Activity ◽  
Protein Signaling ◽  
Stimulation Of

Modulation of Transducin GTPase Activity by Chimeric RGS16 and RGS9 Regulators of G Protein Signaling and the Effector Molecule†

Biochemistry ◽  
1999 ◽  
Vol 38 (16) ◽  
pp. 4931-4937 ◽  
Author(s):  
Randall L. McEntaffer ◽  
Michael Natochin ◽  
Nikolai O. Artemyev
Keyword(s):  
G Protein ◽  
G Protein Signaling ◽  
Gtpase Activity ◽  
Protein Signaling ◽  
Effector Molecule

The G protein signaling regulator RGS3 enhances the GTPase activity of KRAS

Science ◽  
2021 ◽  
Vol 374 (6564) ◽  
pp. 197-201 ◽  
Author(s):  
Chuanchuan Li ◽  
Alberto Vides ◽  
Dongsung Kim ◽  
Jenny Y. Xue ◽  
Yulei Zhao ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Signaling ◽  
Gtpase Activity ◽  
Protein Signaling

scholarly journals Identification of Critical Residues in Gα13for Stimulation of p115RhoGEF Activity and the Structure of the Gα13-p115RhoGEF Regulator of G Protein Signaling Homology (RH) Domain Complex

2011 ◽  
Vol 286 (23) ◽  
pp. 20625-20636 ◽  
Author(s):  
Nicole Hajicek ◽  
Mutsuko Kukimoto-Niino ◽  
Chiemi Mishima-Tsumagari ◽  
Christina R. Chow ◽  
Mikako Shirouzu ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Critical Residues ◽  
Stimulation Of

Metabolic Acidosis Regulates RGS16 and G-protein Signaling in Osteoblasts

2021 ◽  
Author(s):  
Nancy S. Krieger ◽  
David A. Bushinsky
Keyword(s):  
Metabolic Acidosis ◽  
Bone Resorption ◽  
G Protein ◽  
Specific Inhibitor ◽  
Osteoclastic Bone Resorption ◽  
G Protein Signaling ◽  
Rgs Proteins ◽  
Mrna Levels ◽  
Protein Signaling ◽  
Stimulation Of

Chronic metabolic acidosis stimulates cell-mediated net calcium efflux from bone mediated by increased osteoblastic cyclooxygenase 2 (COX2), leading to prostaglandin E2-induced stimulation of RANKL-induced osteoclastic bone resorption. The osteoblastic H+-sensing G-protein coupled receptor (GPCR), OGR1, is activated by acidosis and leads to increased bne resorption. As regulators of G protein signaling (RGS) proteins limit GPCR signaling, we tested whether RGS proteins themselves are regulated by metabolic acidosis. Primary osteoblasts were isolated from neonatal mouse calvariae and incubated in physiological neutral (NTL) or acidic (MET) medium. Cells were collected and RNA extracted for real time PCR analysis with mRNA levels normalized to RPL13a. RGS1, RGS2, RGS3, RGS4, RGS10, RGS11 or RGS18mRNA did not differ between MET and NTL; however by 30' MET decreased RGS16 which persisted for 60' and 3h. Incubation of osteoblasts with the OGR1 inhibitor CuCl2 inhibited the MET induced increase in RGS16 mRNA. Gallein, a specific inhibitor of Gβγ signaling, was used to determine if downstream signaling by the βγ subunit was critical for the response to acidosis. Gallein decreased net Ca efflux from calvariae and COX2 and RANKL gene expression from isolated osteoblasts. These results indicate that regulation of RGS16 plays an important role in modulating the response of the osteoblastic GPCR, OGR1, to metabolic acidosis and subsequent stimulation of osteoclastic bone resorption.

Loss of Gs Activity in Platelets from Carriers with a Heterozygous Missense Mutation in the Regulator of G Protein Signaling 2 (RGS2)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2861-2861 ◽  
Author(s):  
Laura Noé ◽  
Kathleen Freson ◽  
Elke Giets ◽  
Chantal Thijs ◽  
Christine Wittevrongel ◽  
...  
Keyword(s):  
Missense Mutation ◽  
G Protein ◽  
Translation Initiation ◽  
Negative Regulator ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Gsα Gene ◽  
Camp Levels ◽  
Stimulation Of

Abstract Regulator of G protein signaling (RGS) proteins stimulate the GTPase activity of Gα subunits of heterotrimeric G proteins, thereby negatively regulating G protein signaling. In this way, RGS2 acts as a negative regulator of Gq and Gi signaling. It has also been described as a negative regulator of Gs signaling, but via a different mechanism. It inhibits the activation of adenylyl cyclase (AC), the target molecule of Gs, by interacting with it. In olfactory neurons, it was shown that RGS2 attenuates activation of AC type III (Sinnarajah et al., Nature 2001), the main AC subtype in platelets. In this study, we describe the first human genetic defect in RGS2 and provide evidence that RGS2 influences the cAMP level in platelets after Gs stimulation. The proposita is an obese 16-year-old girl with borderline IQ, hirsutism and an increased bone alkaline phosphatase. These symptoms are similar to features of Albright hereditary osteodystrophy, due to heterozygous inactivating mutations in the Gsα gene. The Gsα gene of the proposita is normal, but she carries a missense mutation in the RGS2 gene, resulting in a Gly to Asp substitution in the conserved residue 23 (G23D). This substitution could also be found in her mother and brother, but not in 200 unrelated normal controls. The family members carrying this mutation present with a relatively low number of platelets (+/−150.000/μL) and an increased mean platelet volume (+/−13 fL) and platelet distribution width (+/−17.5 %). Also, platelet function is affected by the mutation. Platelet aggregation is normal in response to all standard agonists, but when the Gs pathway is challenged in their platelets, high levels of different Gs agonists are needed to get inhibition of aggregation in comparison to controls or the father. We also measured cAMP levels in platelets and found that stimulation of the Gs coupled receptors with Gs agonists produced less cAMP in the affected family members. The functional relevance of the mutation was further studied in vitro in HEK293 and MEG-01 cells transfected with wildtype RGS2 and RGS2-G23D. cAMP levels were measured at different time points after stimulation of these cells with Gs agonists. These measurements show that cAMP levels are lower in cells transfected with RGS2-G23D, compared to wildtype RGS2. This indicates that the reduction in cAMP levels found in the platelets of the affected members, is a functional consequence of the mutation. To understand why this mutation leads to an altered function of RGS2, we studied the effect of the mutation at the protein level. Recently, it was shown that there are 4 different translation initiation sites in the RGS2 mRNA, giving rise to 4 proteins with different functional characteristics (Gu et al., Mol Pharmacol 2008). An in vitro transcriptiontranslation assay showed that the presence of the mutation results in a different protein expression profile. We excluded a difference in posttranslational modifications to be the cause of this divergent pattern. The G23D mutation is located in the proximity of 2 of the different translation initiation sites and its presence alters the use of these sites. This results in a different expression profile of the functionally different RGS2 proteins. In conclusion, we present the first platelet Gs signaling defect due to an RGS2 mutation associated with aberrant RGS2 translation.

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