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.

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.

scholarly journals Roles of G Protein-Coupled Receptors (GPCRs) in Gastrointestinal Cancers: Focus on Sphingosine 1-Shosphate Receptors, Angiotensin II Receptors, and Estrogen-Related GPCRs

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2988
Author(s):  
Zhen Zeng ◽  
Chunxiang Ma ◽  
Kexin Chen ◽  
Mingshan Jiang ◽  
Reshma Vasu ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Angiotensin Ii Receptors ◽  
Biological Processes ◽  
Substantial Evidence ◽  
Sphingosine 1 Phosphate ◽  
Gi Cancers ◽  
G Protein Coupled ◽  
Made In

It is well established that gastrointestinal (GI) cancers are common and devastating diseases around the world. Despite the significant progress that has been made in the treatment of GI cancers, the mortality rates remain high, indicating a real need to explore the complex pathogenesis and develop more effective therapeutics for GI cancers. G protein-coupled receptors (GPCRs) are critical signaling molecules involved in various biological processes including cell growth, proliferation, and death, as well as immune responses and inflammation regulation. Substantial evidence has demonstrated crucial roles of GPCRs in the development of GI cancers, which provided an impetus for further research regarding the pathophysiological mechanisms and drug discovery of GI cancers. In this review, we mainly discuss the roles of sphingosine 1-phosphate receptors (S1PRs), angiotensin II receptors, estrogen-related GPCRs, and some other important GPCRs in the development of colorectal, gastric, and esophageal cancer, and explore the potential of GPCRs as therapeutic targets.

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.

RGS18 is a myeloerythroid lineage-specific regulator of G-protein-signalling molecule highly expressed in megakaryocytes

2001 ◽  
Vol 359 (1) ◽  
pp. 109-118 ◽  
Author(s):  
David YOWE ◽  
Nadine WEICH ◽  
Mercy PRABHUDAS ◽  
Louis POISSON ◽  
Patrick ERRADA ◽  
...  
Keyword(s):  
G Protein ◽  
K562 Cells ◽  
Mitogen Activated Protein Kinase ◽  
Yeast Cells ◽  
Rgs Proteins ◽  
Hek 293 ◽  
Lymphoid Lineage ◽  
Cytokines And Chemokines ◽  
G Protein Signalling

Myelopoiesis and lymphopoiesis are controlled by haematopoietic growth factors, including cytokines, and chemokines that bind to G-protein-coupled receptors (GPCRs). Regulators of G-protein signalling (RGSs) are a protein family that can act as GTPase-activating proteins for Gαi- and Gαq-class proteins. We have identified a new member of the R4 subfamily of RGS proteins, RGS18. RGS18 contains clusters of hydrophobic and basic residues, which are characteristic of an amphipathic helix within its first 33 amino acids. RGS18 mRNA was most highly abundant in megakaryocytes, and was also detected specifically in haematopoietic progenitor and myeloerythroid lineage cells. RGS18 mRNA was not detected in cells of the lymphoid lineage. RGS18 was also highly expressed in mouse embryonic 15-day livers, livers being the principal organ for haematopoiesis at this stage of fetal development. RGS1, RGS2 and RGS16, other members of the R4 subfamily, were expressed in distinct progenitor and mature myeloerythroid and lymphoid lineage blood cells. RGS18 was shown to interact specifically with the Gαi-3 subunit in membranes from K562 cells. Furthermore, overexpression of RGS18 inhibited mitogen-activated-protein kinase activation in HEK-293/chemokine receptor 2 cells treated with monocyte chemotactic protein-1. In yeast cells, RGS18 overexpression complemented a pheromone-sensitive phenotype caused by mutations in the endogeneous yeast RGS gene, SST2. These data demonstrated that RGS18 was expressed most highly in megakaryocytes, and can modulate GPCR pathways in both mammalian and yeast cells in vitro. Hence RGS18 might have an important role in the regulation of megakaryocyte differentiation and chemotaxis.

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