Dopamine Receptor Type 2 and Ghrelin Receptor Coexpression Alters CaV2.2 Modulation by G Protein Signaling Cascades

Regulator of G protein Signaling, or RGS, proteins serve an important regulatory role in signaling mediated by G protein-coupled receptors (GPCRs). They all share a common RGS domain that directly interacts with active, GTP-bound Gα subunits of heterotrimeric G proteins. RGS proteins stabilize the transition state for GTP hydrolysis on Gα and thus induce a conformational change in the Gα subunit that accelerates GTP hydrolysis, thereby effectively turning off signaling cascades mediated by GPCRs. This GTPase accelerating protein (GAP) activity is the canonical mechanism of action for RGS proteins, although many also possess additional functions and domains. RGS proteins are divided into four families, R4, R7, R12 and RZ based on sequence homology, domain structure as well as specificity towards Gα subunits. For reviews on RGS proteins and their potential as therapeutic targets, see e.g. [160, 377, 411, 415, 416, 512, 519, 312, 6].

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Differential Modulation of Cardiac Sympathetic Neural Control and β-Adrenoceptor–G Protein Signaling Cascade in Rats With Type 1 and Type 2 Diabetes: Figure 1

Diabetes ◽

10.2337/db15-0503 ◽

2015 ◽

Vol 64 (8) ◽

pp. 2708-2710 ◽

Cited By ~ 1

Author(s):

Yuichi Hattori ◽

Kohshi Hattori ◽

Tokiko Suzuki

Keyword(s):

Type 2 Diabetes ◽

G Protein ◽

Neural Control ◽

Signaling Cascade ◽

G Protein Signaling ◽

Protein Signaling ◽

Differential Modulation

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Regulators of G protein Signaling (RGS) proteins (version 2020.5) in the IUPHAR/BPS Guide to Pharmacology Database

IUPHAR/BPS Guide to Pharmacology CITE ◽

10.2218/gtopdb/f891/2020.5 ◽

2020 ◽

Vol 2020 (5) ◽

Author(s):

Katelin E. Ahlers-Dannen ◽

Mohammed Alqinyah ◽

Christopher Bodle ◽

Josephine Bou Dagher ◽

Bandana Chakravarti ◽

...

Keyword(s):

G Protein ◽

G Protein Coupled Receptors ◽

Signaling Cascades ◽

G Protein Signaling ◽

Rgs Proteins ◽

Protein Signaling ◽

Heterotrimeric G Proteins ◽

Gtp Hydrolysis ◽

Rgs Domain ◽

G Protein Coupled

Regulator of G protein Signaling, or RGS, proteins serve an important regulatory role in signaling mediated by G protein-coupled receptors (GPCRs). They all share a common RGS domain that directly interacts with active, GTP-bound Gα subunits of heterotrimeric G proteins. RGS proteins stabilize the transition state for GTP hydrolysis on Gα and thus induce a conformational change in the Gα subunit that accelerates GTP hydrolysis, thereby effectively turning off signaling cascades mediated by GPCRs. This GTPase accelerating protein (GAP) activity is the canonical mechanism of action for RGS proteins, although many also possess additional functions and domains. RGS proteins are divided into four families, R4, R7, R12 and RZ based on sequence homology, domain structure as well as specificity towards Gα subunits. For reviews on RGS proteins and their potential as therapeutic targets, see e.g. [183, 411, 446, 450, 451, 558, 566, 345, 9].

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Regulators of G protein Signaling (RGS) proteins in GtoPdb v.2021.2

IUPHAR/BPS Guide to Pharmacology CITE ◽

10.2218/gtopdb/f891/2021.2 ◽

2021 ◽

Vol 2021 (2) ◽

Author(s):

Katelin E. Ahlers-Dannen ◽

Mohammed Alqinyah ◽

Christopher Bodle ◽

Josephine Bou Dagher ◽

Bandana Chakravarti ◽

...

Keyword(s):

G Protein ◽

G Protein Coupled Receptors ◽

Signaling Cascades ◽

G Protein Signaling ◽

Rgs Proteins ◽

Protein Signaling ◽

Heterotrimeric G Proteins ◽

Gtp Hydrolysis ◽

Rgs Domain ◽

G Protein Coupled

Regulator of G protein Signaling, or RGS, proteins serve an important regulatory role in signaling mediated by G protein-coupled receptors (GPCRs). They all share a common RGS domain that directly interacts with active, GTP-bound Gα subunits of heterotrimeric G proteins. RGS proteins stabilize the transition state for GTP hydrolysis on Gα and thus induce a conformational change in the Gα subunit that accelerates GTP hydrolysis, thereby effectively turning off signaling cascades mediated by GPCRs. This GTPase accelerating protein (GAP) activity is the canonical mechanism of action for RGS proteins, although many also possess additional functions and domains. RGS proteins are divided into four families, R4, R7, R12 and RZ based on sequence homology, domain structure as well as specificity towards Gα subunits. For reviews on RGS proteins and their potential as therapeutic targets, see e.g. [225, 529, 578, 583, 584, 742, 753, 444, 10].

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The Increased Expression of Regulator of G-Protein Signaling 2 (RGS2) Inhibits Insulin-Induced Akt Phosphorylation and Is Associated with Uncontrolled Glycemia in Patients with Type 2 Diabetes

Metabolites ◽

10.3390/metabo11020091 ◽

2021 ◽

Vol 11 (2) ◽

pp. 91

Author(s):

J. Gustavo Vazquez-Jimenez ◽

M. Stephanie Corpus-Navarro ◽

J. Miguel Rodriguez-Chavez ◽

Hiram J. Jaramillo-Ramirez ◽

Judith Hernandez-Aranda ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

G Protein ◽

Umbilical Vein ◽

Saturated Fatty Acids ◽

Principal Component ◽

G Protein Signaling ◽

Protein Signaling ◽

Resistance State

Experimental evidence in mice models has demonstrated that a high regulator of G-protein signaling 2 (RSG2) protein levels precede an insulin resistance state. In the same context, a diet rich in saturated fatty acids induces an increase in RGS2 protein expression, which has been associated with decreased basal metabolism in mice; however, the above has not yet been analyzed in humans. For this reason, in the present study, we examined the association between RGS2 expression and insulin resistance state. The incubation with palmitic acid (PA), which inhibits insulin-mediated Akt Ser473 phosphorylation, resulted in the increased RGS2 expression in human umbilical vein endothelial-CS (HUVEC-CS) cells. The RGS2 overexpression without PA was enough to inhibit insulin-mediated Akt Ser473 phosphorylation in HUVEC-CS cells. Remarkably, the platelet RGS2 expression levels were higher in type 2 diabetes mellitus (T2DM) patients than in healthy donors. Moreover, an unbiased principal component analysis (PCA) revealed that RGS2 expression level positively correlated with glycated hemoglobin (HbA1c) and negatively with age and high-density lipoprotein cholesterol (HDL) in T2DM patients. Furthermore, PCA showed that healthy subjects segregated from T2DM patients by having lower levels of HbA1c and RGS2. These results demonstrate that RGS2 overexpression leads to decreased insulin signaling in a human endothelial cell line and is associated with poorly controlled diabetes.

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