Enteroviruses and risk of islet autoimmunity or type 1 diabetes: systematic review and meta-analysis of controlled observational studies detecting viral nucleic acids and proteins.

Background: Enteroviruses are routinely detected with molecular methods within large cohorts that are at risk of type 1 diabetes. We aimed to examine the association between enteroviruses and either islet autoimmunity or type 1 diabetes.

Methods: For this systematic review and meta-analysis, we searched PubMed and Embase for controlled observational studies from inception until Jan 1, 2023.

RGS2 inhibits beta-adrenergic receptor-induced cardiomyocyte hypertrophy.

The chronic stimulation of certain G protein-coupled receptors promotes cardiomyocyte hypertrophy and thus plays a pivotal role in the development of human heart failure. The beta-adrenergic receptors (beta-AR) are unique among these in that they signal via Gs, whereas others, such as the alpha1-adrenergic (alpha1-AR) and endothelin-1 (ET-1) receptors, predominantly act through Gq. In this study, we investigated the potential role of regulator of G protein signalling 2 (RGS2) in modulating the hypertrophic effects of the beta-AR agonist isoproterenol (ISO) in rat neonatal ventricular cardiomyocytes.

Up-regulation of endogenous RGS2 mediates cross-desensitization between Gs and Gq signaling in osteoblasts.

Regulator of G protein signaling (RGS) proteins limit G protein signals. In this study, we investigated the role of RGS2 in the control of G protein signaling cascades in osteoblasts, the cells responsible for bone formation. Expression of RGS2 was up-regulated in primary cultures of mouse calvarial osteoblasts by parathyroid hormone-related peptide (PTHrP)-(1-34), which stimulates G(s) signaling.

RGS2 is upregulated by and attenuates the hypertrophic effect of alpha1-adrenergic activation in cultured ventricular myocytes.

Regulator of G protein signaling (RGS) proteins counter the effects of G protein-coupled receptors (GPCRs) by limiting the abilities of G proteins to propagate signals, although little is known concerning their role in cardiac pathophysiology. We investigated the potential role of RGS proteins on alpha1-adrenergic receptor signals associated with hypertrophy in primary cultures of neonatal rat cardiomyocytes. Levels of mRNA encoding RGS proteins 1-5 were examined, and the alpha1-adrenergic agonist phenylephrine (PE) significantly increased RGS2 gene expression but had little or no effect on the others.

RGS proteins have a signalling complex: interactions between RGS proteins and GPCRs, effectors, and auxiliary proteins.

The intracellular regulator of G protein signalling (RGS) proteins were first identified as GTPase activating proteins (GAPs) for heterotrimeric G proteins, however, it was later found that they can also regulate G protein-effector interactions in other ways that are still not well understood. There is increasing evidence that some of the effects of RGS proteins occur due to their ability to interact with multiprotein signalling complexes. In this review, we will discuss recent evidence that supports the idea that RGS proteins can bind to proteins other than Galpha, such as G protein coupled receptors (GPCRs, e.

RGS2 interacts with Gs and adenylyl cyclase in living cells.

Regulator of G Protein Signalling (RGS) proteins impede heterotrimeric G protein signalling. RGS2 decreases cAMP production and appears to interact with both adenylyl cyclase (AC) and its stimulatory G protein Gs. We showed previously that Green Fluorescent Protein-tagged RGS2 (GFP-RGS2) localizes to the nucleus in HEK 293 cells and is recruited to the plasma membrane when co-expressed with Gsalpha, or the Gs-coupled beta2-adrenergic receptor (beta2AR).

Recruitment of RGS2 and RGS4 to the plasma membrane by G proteins and receptors reflects functional interactions.

N-terminally green fluorescent protein (GFP)-tagged regulator of G protein signaling (RGS) 2 and RGS4 fusion proteins expressed in human embryonic kidney 293 cells localized to the nucleus and cytosol, respectively. They were selectively recruited to the plasma membrane by G proteins and correspondingly by receptors that activate those G proteins: GFP-RGS2 when coexpressed with Galphas, beta2-adrenergic receptor, Galphaq, or AT1A angiotensin II receptor, and GFP-RGS4 when coexpressed with Galphai2 or M2 muscarinic receptor. G protein mutants with reduced RGS affinity did not produce this effect, implying that the recruitment involves direct binding to G proteins and is independent of downstream signaling events.

Activity, regulation, and intracellular localization of RGS proteins.

RGS proteins attenuate the activities of heterotrimeric G proteins largely by promoting the hydrolysis of the activating nucleotide GTP. This review discusses the interactions of RGS proteins and G proteins and how those interactions are regulated by a variety of factors including auxiliary proteins and other cellular constituents, posttranslational modifications, and intracellular localization patterns. In addition, we discuss progress that has been made toward understanding the roles that RGS proteins play in vivo, and how they may serve to govern responses to G protein-coupled receptors upon acute and prolonged activation by agonists.