scholarly journals The dynamic role of regulator of G-protein signalling (RGS) proteins in partial agonism

2014 ◽  
Vol 592 (17) ◽  
pp. 3701-3702
Author(s):  
Joobin Sattar ◽  
Kevin P. Grace ◽  
Guillaume Bastin
Keyword(s):  
G Protein ◽  
Rgs Proteins ◽  
Partial Agonism ◽  
G Protein Signalling

scholarly journals The Downstream Regulation of Chemokine Receptor Signalling: Implications for Atherosclerosis

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Jyoti Patel ◽  
Keith M. Channon ◽  
Eileen McNeill
Keyword(s):  
G Protein ◽  
Chemokine Receptors ◽  
Vascular Inflammation ◽  
Vascular Wall ◽  
Rgs Proteins ◽  
Cell Recruitment ◽  
Physiological Processes ◽  
G Protein Signalling ◽  
Atherosclerotic Plaque Formation ◽  
G Protein Coupled

Heterotrimeric G-protein-coupled receptors (GPCRs) are key mediators of intracellular signalling, control numerous physiological processes, and are one of the largest class of proteins to be pharmacologically targeted. Chemokine-induced macrophage recruitment into the vascular wall is an early pathological event in the progression of atherosclerosis. Leukocyte activation and chemotaxis during cell recruitment are mediated by chemokine ligation of multiple GPCRs. Regulation of GPCR signalling is critical in limiting vascular inflammation and involves interaction with downstream proteins such as GPCR kinases (GRKs), arrestin proteins and regulator of G-protein signalling (RGS) proteins. These have emerged as new mediators of atherogenesis by functioning in internalisation, desensitisation, and signal termination of chemokine receptors. Targeting chemokine signalling through these proteins may provide new strategies to alter atherosclerotic plaque formation and plaque biology.

RGS-Insensitive G-Protein Mutations to Study the Role of Endogenous RGS Proteins

2004 ◽  
pp. 229-243 ◽  
Author(s):  
Ying Fu ◽  
Huailing Zhong ◽  
Masakatsu Nanamori ◽  
Richard M Mortensen ◽  
Xinyan Huang ◽  
...  
Keyword(s):  
G Protein ◽  
Rgs Proteins ◽  
Protein Mutations

scholarly journals RGS14 is a novel Rap effector that preferentially regulates the GTPase activity of Gαo

2000 ◽  
Vol 350 (1) ◽  
pp. 19-29 ◽  
Author(s):  
Sabine TRAVER ◽  
Carole BIDOT ◽  
Nathalie SPASSKY ◽  
Tania BALTAUSS ◽  
Marie-France DE TAND ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
G Protein ◽  
Rgs Proteins ◽  
Gtpase Activity ◽  
Α Subunit ◽  
Adult Mice ◽  
G Protein Signalling ◽  
Marked Preference

In an attempt to elucidate the physiological function(s) of the Ras-related Rap proteins, we used the yeast two-hybrid system and isolated a cDNA encoding a protein that interacts with both Rap1 and Rap2, but not with Ras; the use of Rap2 mutants showed that this interaction is characteristic of a potential Rap effector. This protein was identified as RGS14, a member of the recently discovered family of RGS (‘regulators of G-protein signalling’) proteins that stimulate the GTPase activity of the GTP-binding α subunit of heterotrimeric G-proteins (Gα). Deletion analysis, as well as in vitro binding experiments, revealed that RGS14 binds Rap proteins through a domain distinct from that carrying the RGS identity, and that this domain shares sequence identity with the Ras/Rap binding domain of B-Raf and Raf-1 kinases. RGS14 is distinguished from other RGS proteins by its marked preference for Gαo over other Gα subunits: RGS14 binds preferentially to Gαo in isolated brain membranes, and also interacts preferentially with Gαo (as compared with Gαi1) to stimulate its GTPase activity. In adult mice, RGS14 expression is restricted to spleen and brain. In situ hybridization studies showed that it is highly expressed only in certain areas of mouse brain (such as the CA1 and CA2 regions of the hippocampus), and that this pattern closely resembles that of Rap2, but not Rap1, expression. Double in situ hybridization experiments revealed that certain cells in the hippocampus express both RGS14 and Gαo, as well as both RGS14 and Rap2, showing that the interaction of RGS14 with Gαo and Rap2 is physiologically possible. Taken together, these results suggest that RGS14 could constitute a bridging molecule that allows cross-regulation of signalling pathways downstream from G-protein-coupled receptors involving heterotrimeric proteins of the Gi/o family and those involving the Ras-related GTPase Rap2.

RGS proteins: identifying new GAPs in the understanding of blood pressure regulation and cardiovascular function

2009 ◽  
Vol 116 (5) ◽  
pp. 391-399 ◽  
Author(s):  
Steven Gu ◽  
Carlo Cifelli ◽  
Sean Wang ◽  
Scott P. Heximer
Keyword(s):  
Blood Pressure ◽  
G Protein ◽  
Uncontrolled Hypertension ◽  
Rgs Proteins ◽  
Treatment And Prevention ◽  
Current State ◽  
G Protein Signalling ◽  
Prevention Of Hypertension ◽  
And Function ◽  
G Protein Coupled

Understanding the mechanisms that underlie BP (blood pressure) variation in humans and animal models may provide important clues for reducing the burden of uncontrolled hypertension in industrialized societies. High BP is often associated with increased signalling via G-protein-coupled receptors. Three members of the RGS (regulator of G-protein signalling) superfamily RGS2, RGS4 and RGS5 have been implicated in the attenuation of G-protein signalling pathways in vascular and cardiac myocytes, as well as cells of the kidney and autonomic nervous system. In the present review, we discuss the current state of knowledge regarding their differential expression and function in cardiovascular tissues, and the likelihood that one or more of these alleles are candidate hypertension genes. Together, findings from the studies described herein suggest that development of methods to modulate the expression and function of RGS proteins may be a possible strategy for the treatment and prevention of hypertension and cardiovascular disease.

loco encodes an RGS protein required for Drosophila glial differentiation

Development ◽  
1999 ◽  
Vol 126 (8) ◽  
pp. 1781-1791 ◽  
Author(s):  
S. Granderath ◽  
A. Stollewerk ◽  
S. Greig ◽  
C.S. Goodman ◽  
C.J. O'Kane ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
G Protein ◽  
Glial Cell ◽  
Glial Cells ◽  
Cell Development ◽  
Rgs Proteins ◽  
Glial Differentiation ◽  
G Protein Signalling ◽  
Rgs Domain ◽  
Longitudinal Axon

In Drosophila, glial cell development depends on the gene glial cells missing (gcm). gcm activates the expression of other transcription factors such as pointed and repo, which control subsequent glial differentiation. In order to better understand glial cell differentiation, we have screened for genes whose expression in glial cells depends on the activity of pointed. Using an enhancer trap approach, we have identified loco as such a gene. loco is expressed in most lateral CNS glial cells throughout development. Embryos lacking loco function have an normal overall morphology, but fail to hatch. Ultrastructural analysis of homozygous mutant loco embryos reveals a severe glial cell differentiation defect. Mutant glial cells fail to properly ensheath longitudinal axon tracts and do not form the normal glial-glial cell contacts, resulting in a disruption of the blood-brain barrier. Hypomorphic loco alleles were isolated following an EMS mutagenesis. Rare escapers eclose which show impaired locomotor capabilities. loco encodes the first two known Drosophila members of the family of Regulators of G-protein signalling (RGS) proteins, known to interact with the alpha subunits of G-proteins. loco specifically interacts with the Drosophila alphai-subunit. Strikingly, the interaction is not confined to the RGS domain. This interaction and the coexpression of LOCO and Galphai suggests a function of G-protein signalling for glial cell development.

scholarly journals GPR158/179 regulate G protein signaling by controlling localization and activity of the RGS7 complexes

2012 ◽  
Vol 197 (6) ◽  
pp. 711-719 ◽  
Author(s):  
Cesare Orlandi ◽  
Ekaterina Posokhova ◽  
Ikuo Masuho ◽  
Thomas A. Ray ◽  
Nazarul Hasan ◽  
...  
Keyword(s):  
G Protein ◽  
Night Vision ◽  
G Protein Signaling ◽  
Rgs Proteins ◽  
Protein Signaling ◽  
Gpcr Signaling ◽  
Signaling Specificity ◽  
Orphan Gpcrs ◽  
G Protein Coupled

The extent and temporal characteristics of G protein–coupled receptor (GPCR) signaling are shaped by the regulator of G protein signaling (RGS) proteins, which promote G protein deactivation. With hundreds of GPCRs and dozens of RGS proteins, compartmentalization plays a key role in establishing signaling specificity. However, the molecular details and mechanisms of this process are poorly understood. In this paper, we report that the R7 group of RGS regulators is controlled by interaction with two previously uncharacterized orphan GPCRs: GPR158 and GPR179. We show that GPR158/179 recruited RGS complexes to the plasma membrane and augmented their ability to regulate GPCR signaling. The loss of GPR179 in a mouse model of night blindness prevented targeting of RGS to the postsynaptic compartment of bipolar neurons in the retina, illuminating the role of GPR179 in night vision. We propose that the interaction of RGS proteins with orphan GPCRs promotes signaling selectivity in G protein pathways.

The Role Of P115 Rhogef In The Rho Mediated Effects Of Lpa On The Actin Cytoskeleton.

1999 ◽  
Vol 5 (S2) ◽  
pp. 1326-1327
Author(s):  
C.L. Schwartz ◽  
C. Wells ◽  
X. Jiang ◽  
H.J. Arnott ◽  
P.C. Sternweis ◽  
...  
Keyword(s):  
G Protein ◽  
Fibroblast Cell ◽  
Stress Fiber ◽  
Fiber Formation ◽  
Rgs Proteins ◽  
Nucleotide Exchange ◽  
Lpa Receptor ◽  
Stress Fiber Formation ◽  
P115 Rhogef

In the fibroblast cell line, 3T3, lysophosphatidic acid (LPA) induces stress fiber formation. Stress fibers participate in physiological functions such as cell motility. LPA acts through a receptor coupled to a PTX-insensitive G-protein, G13. It was shown that a constitutively activated mutant of α13 (Q226L) induces stress fiber formation in Swiss3T3 cells through a second messenger cascade that involves a monomeric G-protein, Rho. The recently discovered guanine nucleotide exchange factor, p115 RhoGEF (p115) forms a link between a n and Rho A. In the presence of α13, p115 activates Rho. The N-terminus of p115 contains a regulator of G-protein signaling (RGS) box. RGS proteins act as negative regulators of G-protein dependent signaling by increasing GTPase activity and “locking” the G-protein in an inactive state. We have tested a role of p115 in the pathway coupling the LPA receptor to stress fiber formation by Rho in NTH-3T3 cells.

scholarly journals G-protein signalling pathways and oestrogen: a role of balanced maintenance in osteoblasts

1999 ◽  
Vol 1449 (3) ◽  
pp. 284-292 ◽  
Author(s):  
Stelios Papaioannou ◽  
Anthony M. Tumber ◽  
Murray C. Meikle ◽  
Fraser McDonald
Keyword(s):  
G Protein ◽  
Signalling Pathways ◽  
G Protein Signalling

scholarly journals The aorta and heart differentially express RGS (regulators of G-protein signalling) proteins that selectively regulate sphingosine 1-phosphate, angiotensin II and endothelin-1 signalling

2003 ◽  
Vol 371 (3) ◽  
pp. 973-980 ◽  
Author(s):  
Hyeseon CHO ◽  
Kathleen HARRISON ◽  
Owen SCHWARTZ ◽  
John H. KEHRL
Keyword(s):  
Angiotensin Ii ◽  
Cardiovascular System ◽  
G Protein ◽  
Differentially Express ◽  
Rgs Proteins ◽  
Cardiovascular Development ◽  
Functional Roles ◽  
Receptor Signalling ◽  
G Protein Signalling ◽  
Sphingosine 1 Phosphate

Normal cardiovascular development and physiology depend in part upon signalling through G-protein-coupled receptors (GPCRs), such as the angiotensin II type 1 (AT1) receptor, sphingosine 1-phosphate (S1P) receptors and endothelin-1 (ET-1) receptor. Since regulator of G-protein signalling (RGS) proteins function as GTPase-activating proteins for the Gα subunit of heterotrimeric G-proteins, these proteins undoubtedly have functional roles in the cardiovascular system. In the present paper, we show that human aorta and heart differentially express RGS1, RGS2, RGS3S (short-form), RGS3L (long-form), PDZ-RGS3 (PDZ domain-containing) and RGS4. The aorta prominently expresses mRNAs for all these RGS proteins except PDZ-RGS3. Various stimuli that are critical for both cardiovascular development and function regulate dynamically the mRNA levels of several of these RGS proteins in primary human aortic smooth muscle cells. Both RGS1 and RGS3 inhibit signalling through the S1P1 (formerly known as EDG-1), S1P2 (formerly known as EDG-5) and S1P3 (formerly known as EDG-3) receptors, whereas RGS2 and RGS4 selectively attenuate S1P2-and S1P3-receptor signalling respectively. All of the tested RGS proteins inhibit AT1-receptor signalling, whereas only RGS3 and, to a lesser extent, RGS4 inhibit ETA-receptor signalling. The conspicuous expression of RGS proteins in the cardiovascular system and their selective effects on relevant GPCR-signalling pathways provide additional evidence that they have functional roles in cardiovascular development and physiology.

Sign in / Sign up

Export Citation Format

Share Document