β adrenergic receptor-mediated atrial specific up-regulation of RGS5

Jean-Baptiste, Gaël; Li, Xiaoyü; Yang, Zhao; Heubach, Jürgen F.; Gaudio, Sabrina; Khoury, Chamel; Ravens, Ursula; Greenwood, Michael T.

doi:10.1016/j.lfs.2004.11.001

Cited by 17 publications

(15 citation statements)

References 52 publications

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“…We have previously generated specific RGS5 antiserum and we have shown that this protein migrates as 23 kDa protein that is abundantly expressed in cardiac and skeletal muscle [18]. Here we continue our analysis of the RGS5 protein and we report a new binding partner for RGS5.…”

Section: Introductionsupporting

confidence: 60%

“…The plasmids encoding the different GPCR C-tails fused to GFP were constructed by first amplifying the receptor C-tails using reverse transcribed RNA that was obtained from mouse tissues (brain, testes or heart) and the following oligos: SST 5 The amplified products were subcloned into p426GAL1-GFP as described above for RGS5. The yeast expression plasmid p425GAL-RGS5 and the mammalian expression plasmid for RGS5 were previously described [18,19]. p426GAL1-ATG-GFP expressing GFP alone under the control of the galactose inducible GAL1 promoter was previously described [20].…”

Section: Introductionmentioning

confidence: 99%

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Evidence for the Dimerization of Human Regulator of G-protein Signalling 5 (RGS5)

Yang

Gaudio

Song

et al. 2007

Cell Physiol Biochem

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RGS5 is a R4 type RGS that regulates GPCR signalling. Using western blot, we detected RGS5 as a specific 23 kDa protein in cells overexpressing RGS5. A 42 kDa band representing a possible RGS5 dimer was also detected. Given that GPCRs and their associated proteins form complexes involving multiple protein-protein interactions, we investigated the possibility that the 42 kDa band represents an RGS5-RGS5 dimer. RGS5 dimerization was confirmed by the analysis of a GFP tagged RGS5 fusion in yeast and with two-hybrid assays. Analysis of RGS5 in HEK293A cells suggests that the dimer may serve a regulatory function since it is longer lived than the monomer.

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Section: Introductionsupporting

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Evidence for the Dimerization of Human Regulator of G-protein Signalling 5 (RGS5)

Yang

Gaudio

Song

et al. 2007

Cell Physiol Biochem

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“…In line with these notions, our data suggest that Rgs5 abrogates Smad 2 phosphorylation and Smad 2/3 translocation in both cultured cardiac fibroblasts and hypertrophied hearts, thus inhibiting collagen synthesis and fibrosis. Recent studies indicate that TGF-β1/Smad signaling can be regulated by MEK-ERK1/2 signaling (9)(10)(11). We therefore examined the effects of MEK-ERK1/2 activation on fibrotic signaling and found that blocking MEK-ERK1/2 activation led to significant inhibition, whereas activation of MEK-ERK1/2 resulted in up-regulation of collagen synthesis and Smad 2/3 signaling.…”

Section: Discussionmentioning

confidence: 96%

“…After it has been activated, p38, JNKs, and ERKs phosphorylate a wide array of intracellular targets, which include numerous transcription factors, resulting in the reprogramming of cardiac gene expression. The role that MEK1-ERK1/2 plays in the regulation of cardiac hypertrophy is an area of ongoing debate (9)(10)(11). It has been shown that ERK1/2 is activated in cultured neonatal rat cardiomyocytes by agonist stimulation (12,13).…”

Section: Discussionmentioning

confidence: 99%

“…Cho et al (7) reported that the hypotensive phenotype may be related to increased NO susceptibility combined with increased and ERK1/2 activation in vascular smooth muscle cells. In the heart, Rgs5 is known to be upregulated in atria tissue of mice that overexpressed β2-adrenergic receptor, as well as in atria of rats that were chronically administered the β-adrenergic agonist isoproterenol (9). However, the role of Rgs5 as a regulator of cardiac hypertrophy and fibrosis has not previously been determined.…”

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confidence: 99%

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Regulator of G protein signaling 5 protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload

Feng

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

121

127

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The development of cardiac hypertrophy in response to increased hemodynamic load and neurohormonal stress is initially a compensatory response that may eventually lead to ventricular dilation and heart failure. Regulator of G protein signaling 5 (Rgs5) is a negative regulator of G protein-mediated signaling by inactivating Gα(q) and Gα(i), which mediate actions of most known vasoconstrictors. Previous studies have demonstrated that Rgs5 expresses among various cell types within mature heart and showed high levels of Rgs5 mRNA in monkey and human heart tissue by Northern blot analysis. However, the critical role of Rgs5 on cardiac remodeling remains unclear. To specifically determine the role of Rgs5 in pathological cardiac remodeling, we used transgenic mice with cardiac-specific overexpression of human Rgs5 gene and Rgs5 −/− mice. Our results demonstrated that the transgenic mice were resistant to cardiac hypertrophy and fibrosis through inhibition of MEK-ERK1/2 signaling, whereas the Rgs5 −/− mice displayed the opposite phenotype in response to pressure overload. These studies indicate that Rgs5 protein is a crucial component of the signaling pathway involved in cardiac remodeling and heart failure.

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Regulatory mechanisms involved in modulating RGS function

Jean-Baptiste

Yang

Greenwood

2006

Cell. Mol. Life Sci.

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Regulator of G-Protein Signaling (RGS) refers to a conserved 120-125 amino acid motif that was first identified by its ability to negatively regulate G-Protein-Coupled Receptor (GPCR) signalling. Mechanistically, RGSs were found to regulate GPCR responses by binding to and stimulating the GTPase activity of the receptor-activated GTP-bound G alpha subunits. There are now over 25 mammalian RGSs containing proteins that are reported to carry out a variety of functions, many of which are unrelated to GPCR signalling. RGS proteins range in size from small proteins that contain little more than an RGS box to very large proteins that contain a variety of domains. The selectivity of function of the RGS proteins is attributable to the divergence of the RGS sequences as well as the presence of a variety of functional motifs, which allow them to interact with other proteins. Here we focus on the RGSs that are involved in modulating GPCR signalling by reviewing the diversity of the mechanisms involved in regulating these RGSs.

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β adrenergic receptor-mediated atrial specific up-regulation of RGS5

Cited by 17 publications

References 52 publications

Evidence for the Dimerization of Human Regulator of G-protein Signalling 5 (RGS5)

Evidence for the Dimerization of Human Regulator of G-protein Signalling 5 (RGS5)

Regulator of G protein signaling 5 protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload

Regulatory mechanisms involved in modulating RGS function

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