Interferonβ-1b Induces the Expression of RGS1 a Negative Regulator of G-Protein Signaling

Tran, Tiffany; Paz, Pedro E.; Velichko, Sharlene; Cifrese, Jill; Belur, Praveen; Yamaguchi, Ken; Ku, Karin; Mirshahpanah, Parham; Reder, Anthony T.; Croze, Ed

doi:10.1155/2010/529376

Cited by 31 publications

(37 citation statements)

References 40 publications

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“…Expression is much higher in T cells from human gut versus peripheral blood, and that this can be exaggerated in intestinal inflammation (87). RGS1 expression is upregulated in many cell types by exposure to hypoxia or interferons (68,88). Reduced RGS1 levels have been shown to enhance T cell, B cell, dendritic, and macrophage responsiveness to chemokines (87,89,90).…”

Section: G-protein Regulatory Proteinsmentioning

confidence: 99%

The impact of RGS and other G-protein regulatory proteins on Gαi-mediated signaling in immunity

Kehrl

2016

Biochemical Pharmacology

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Leukocyte chemoattractant receptors are members of the G-protein coupled receptor (GPCR) family. Signaling downstream of these receptors directs the localization, positioning and homeostatic trafficking of leukocytes; as well as their recruitment to, and their retention at, inflammatory sites. Ligand induced changes in the molecular conformation of chemoattractant receptors results in the engagement of heterotrimeric G-proteins, which promotes α subunits to undergo GTP/GDP exchange. This results in the functionally release of βγ subunits from the heterotrimers, thereby activating downstream effector molecules, which initiate leukocyte polarization, gradient sensing, and directional migration. Pertussis toxin ADP ribosylates Gαi subunits and prevents chemoattractant receptors from triggering Gαi nucleotide exchange. The use of pertussis toxin revealed the essential importance of Gαi subunit nucleotide exchange for chemoattractant receptor signaling. More recent studies have identified a range of regulatory mechanisms that target these receptors and their associated heterotrimeric G-proteins, thereby helping to control the magnitude, kinetics, and duration of signaling. A failure in these regulatory pathways can lead to impaired receptor signaling and immunopathology. The analysis of mice with targeted deletions of Gαi isoforms as well as some of these G-protein regulatory proteins is providing insights into their roles in chemoattractant receptor signaling.

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Section: G-protein Regulatory Proteinsmentioning

confidence: 99%

The impact of RGS and other G-protein regulatory proteins on Gαi-mediated signaling in immunity

Kehrl

2016

Biochemical Pharmacology

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“…1) and are induced in response to interferon (IFN)-γ therapy in early treatment on day 1 (NCBI GEO database, accession number GDS2419). Tran et al reported that IFN-γ induced RGS1 mRNA and protein expression in PBMC from human MS patients as early as 4 h after treatment (26). However, the role of RGS1 in the onset or progression of MS has never been explored.…”

Section: Rgs1 and Msmentioning

confidence: 99%

Regulator of G-protein Signaling (RGS)1 and RGS10 Proteins as Potential Drug Targets for Neuroinflammatory and Neurodegenerative Diseases

Lee

Dagher

2016

AAPS J

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Abstract. Regulator of G-protein signaling (RGS) proteins were originally identified as negative regulators of G-protein-coupled receptor (GPCR) signaling via their GTPase-accelerating protein (GAP) activity. All RGS proteins contain evolutionarily conserved RGS domain; however, they differ in their size and regulatory domains. RGS1 and RGS10 are smaller than other RGS proteins, and their functions involve various inflammatory responses including autoimmune responses in both the periphery and the central nervous system (CNS). Neuroinflammation is the chronic inflammatory response in the CNS. Acute inflammatory response in the CNS is believed to be beneficial by involving the neuroprotective actions of immune cells in the brain, particularly microglia, to limit tissue damage and to aid in neuronal repair. However, chronically elevated levels of cytokines serve to maintain activation of abundant numbers of immune cells potentiating prolonged inflammatory responses and creating an environment of oxidative stress, which further hastens oxidative damage of neurons. In this review, we describe the implications and features of RGS proteins (specifically RGS1 and RGS10) in neuroinflammation and neurodegenerative diseases. We will discuss the experimental and epidemiological evidence on the benefits of anti-inflammatory interventions by targeting RGS1 and/or RGS10 protein function or expression in order to delay or attenuate the progression of neurodegeneration, particularly in multiple sclerosis (MS) and Parkinson's disease (PD).

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“…The latter allele also conferred susceptibility to celiac disease, a chronic GI inflammatory disease associated with sensitivity to gluten (42). Although RGS1 expression was similar in peripheral blood mononuclear cells (PBMCs) from patients with MS and controls (48), a separate study showed that modulation of RGS1 expression by interferon-β (IFN-β), a standard treatment for MS (49,50). RGS1 was also upregulated in diseasepromoting T H 17 cells isolated from the CNS of mice in a model of human MS, experimental autoimmune encephalomyelitis (EAE) (51).…”

Section: −/− (T and B Cell-deficient) Mice Receiving T Cells From Rgs1mentioning

confidence: 99%

R4 Regulator of G Protein Signaling (RGS) Proteins in Inflammation and Immunity

Xie

Chan

Druey

2015

AAPS J

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Abstract. G protein-coupled receptors (GPCRs) have important functions in both innate and adaptive immunity, with the capacity to bridge interactions between the two arms of the host responses to pathogens through direct recognition of secreted microbial products or the by-products of host cells damaged by pathogen exposure. In the mid-1990s, a large group of intracellular proteins was discovered, the regulator of G protein signaling (RGS) family, whose main, but not exclusive, function appears to be to constrain the intensity and duration of GPCR signaling. The R4/B subfamily-the focus of this review-includes 8,13,16,18, and 21, which are the smallest RGS proteins in size, with the exception of RGS3. Prominent roles in the trafficking of B and T lymphocytes and macrophages have been described for RGS1, RGS13, and RGS16, while RGS18 appears to control platelet and osteoclast functions. Additional G protein independent functions of RGS13 have been uncovered in gene expression in B lymphocytes and mast cell-mediated allergic reactions. In this review, we discuss potential physiological roles of this RGS protein subfamily, primarily in leukocytes having central roles in immune and inflammatory responses. We also discuss approaches to target RGS proteins therapeutically, which represents a virtually untapped strategy to combat exaggerated immune responses leading to inflammation.

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Interferonβ-1b Induces the Expression of RGS1 a Negative Regulator of G-Protein Signaling

Cited by 31 publications

References 40 publications

The impact of RGS and other G-protein regulatory proteins on Gαi-mediated signaling in immunity

The impact of RGS and other G-protein regulatory proteins on Gαi-mediated signaling in immunity

Regulator of G-protein Signaling (RGS)1 and RGS10 Proteins as Potential Drug Targets for Neuroinflammatory and Neurodegenerative Diseases

R4 Regulator of G Protein Signaling (RGS) Proteins in Inflammation and Immunity

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