Disease relevance of Rgs2

• 5. Bordetella pertussis toxin completely abolished ACh-mediated current amplification of GIRK channels coexpressed with or without RGS2 [1].
• By diminishing cGK activity, endothelial dysfunction may impair RGS2 activation, thereby blunting vascular relaxation and contributing to hypertension [2].

Psychiatry related information on Rgs2

• In the Fmr1 knockout mice, a model for fragile X mental retardation syndrome, the levels of regulator of G-protein signaling (Rgs) 4 but not Rgs2 mRNA were considerably reduced (65% from control) in the cerebral cortex and hippocampal CA1 region [3].

High impact information on Rgs2

• We also show that this locus can be subdivided into three regions, one of which contains Rgs2, which encodes a regulator of G protein signaling [4].
• Genetic dissection of a behavioral quantitative trait locus shows that Rgs2 modulates anxiety in mice [4].
• Rgs2-/- mice develop marked hypertension, and their blood vessels show enhanced contraction and decreased cGMP-mediated relaxation [5].
• Our study shows that RGS-2 is required for normal vascular function and blood pressure and is a new drug development target for hypertension [5].
• When expressed in Xenopus laevis oocytes, SPL markedly increased inhibition of alpha-adrenergic receptor (alphaAR) Ca2+ signalling by RGS2 [6].

Biological context of Rgs2

• Within the pituitary, Rgs2 was expressed in undifferentiated cells, and was downregulated at the completion of the hormone cell differentiation [7].
• CD40 signaling, by contrast, fails to cause rapid up-regulation of RGS1 or RGS2 [8].
• Both rgs2+/- and rgs2-/- mice exhibited a strong hypertensive phenotype, renovascular abnormalities, persistent constriction of the resistance vasculature, and prolonged response of the vasculature to vasoconstrictors in vivo [9].
• Analysis of P2Y receptor-mediated Ca2+ signaling in vascular smooth muscle cells in vitro indicated that loss of RGS2 increased agonist potency and efficacy and slowed the kinetics of signal termination [9].
• RGS2, a GTPase-activating protein for Gqalpha that is critical for blood pressure homeostasis, has been suggested to serve as an effector of the NO-cGMP pathway that promotes vascular relaxation based on studies of aortic rings in vitro [10].

Anatomical context of Rgs2

• One gene that was up-regulated at later stages of chondrocyte differentiation was Rgs2 [11].
• Overexpression of Rgs2 in the chondrogenic cell line ATDC5 resulted in accelerated hypertrophic differentiation, thus providing functional validation of microarray data [11].
• Regulation of T cell activation, anxiety, and male aggression by RGS2 [12].
• We inhibited endogenous Galphaq function by single cell microinjection of anti-Galphaq/11 antibody or RGS2 protein (a GAP protein for Galphaq), followed by immunostaining to assess GLUT4 translocation in 3T3-L1 adipocytes [13].
• The result of these adaptive mechanisms was the reduced excitability of Ca(2+) signaling, as reflected by the markedly reduced response of RGS2(-/-) cells to changes in the endoplasmic reticulum Ca(2+) load and to an increase in extracellular Ca(2+) [14].

Associations of Rgs2 with chemical compounds

• By contrast, RGS2 inhibited the response to carbachol and CCK with equal potency [15].
• Hypertension and prolonged vasoconstrictor signaling in RGS2-deficient mice [9].
• Galphaq/11 antibody and RGS2 inhibited insulin-induced GLUT4 translocation by 60 or 75%, respectively, indicating that activated Galphaq is important for insulin-induced glucose transport [13].
• Deletion of RGS2 modified the kinetic of inositol 1,4,5-trisphosphate (IP(3)) production without affecting the peak level of IP(3), but rather increased the steady-state level of IP(3) at all agonist concentrations [14].
• The angiotensin II-stimulated Ca mobilization and ERK1/2 phosphorylation were negatively correlated with RGS2 mRNA expression [16].

Regulatory relationships of Rgs2

• Sarco/endoplasmic reticulum Ca(2+) ATPase 2b was up-regulated to more rapidly remove Ca(2+) from the cytosol of RGS2(-/-) cells [14].
• Parathyroid hormone induces RGS-2 expression by a cyclic adenosine 3',5'-monophosphate-mediated pathway in primary neonatal murine osteoblasts [17].

Other interactions of Rgs2

• Furthermore, overexpression of the osteoblast-specific transcription factor Runx2 also led to a stimulation of RGS-2 promoter activity [18].
• RGS2: a "turn-off" in hypertension [19].

Analytical, diagnostic and therapeutic context of Rgs2

• Quantitative mRNA and protein RGS2 expression were performed by real-time quantitative reverse transcriptase-polymerase chain reaction and by immunoblotting, respectively [16].
• Polymorphism (C1114G) in the 3' untranslated region of the RGS2 gene was investigated by direct sequencing and real-time polymerase chain reaction (PCR) [16].
• We found that 10 nmol/L PTH maximally induced RGS-2 mRNA in murine MC3T3-E1 cells, rat Py1a and ROS-17/2.8 cells, primary mouse osteoblasts (MOB cells), and mouse calvariae organ culture at 1-2 h posttreatment [17].
• In situ hybridization indicated that the RGS2 mRNA was expressed in the granulosa layer of mature follicles [20].

References