scholarly journals Spatiotemporal Changes in the Gene Expression Spectrum of the β2 Adrenergic Receptor Signaling Pathway in the Lungs of Rhesus Monkeys

Lung ◽  
2021 ◽  
Vol 199 (1) ◽  
pp. 73-82
Author(s):  
Zhongmei Zheng ◽  
Bangrong Cao ◽  
Yu Hu ◽  
Liang Xie ◽  
Ling Gu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathway ◽  
G Protein ◽  
Adrenergic Receptor ◽  
Rhesus Monkeys ◽  
Developmental Process ◽  
Spatiotemporal Changes ◽  
Neonatal Stage ◽  
Β2 Adrenergic Receptor ◽  
Key Genes

Abstract Objective β2 adrenergic receptor (ADRB2) agonists mainly participate in regulation of airway function through the ADRB2-G protein-adenylyl cyclase (AC) signaling pathway; however, the key genes associated with this pathway and the spatiotemporal changes in the expression spectrum of some of their subtypes remain unclear, resulting in an insufficient theoretical basis for formulating the dose and method of drug administration for neonates. Methods We performed sampling at different developmental time points in rhesus monkeys, including the embryo stage, neonatal stage, and adolescence. The MiSeq platform was used for sequencing of key genes and some of their subtypes in the ADRB2 signaling pathway in lung tissues, and target gene expression was normalized and calculated according to reads per kilobase million. Results At different lung-developmental stages, we observed expression of phenylethanolamine N-methyltransferase (PNMT), ADRB2, AC, AKAP and EPAC subtypes (except AC8, AKAP4/5), and various phosphodiesterase (PDE) subtypes (PDE3, PDE4, PDE7, and PDE8), with persistently high expression of AC6, PDE4B, and AKAP(1/2/8/9/12/13, and EZR) maintained throughout the lung-developmental process, PNMT, ADRB2, AC(4/6), PDE4B, and AKAP(1/2/8/9/12/13, EZR, and MAP2)were highly expressed at the neonatal stage. Conclusion During normal lung development in rhesus monkeys, key genes associated with ADRB2–G protein–AC signaling and some of their subtypes are almost all expressed at the neonatal stage, suggesting that this signaling pathway plays a role in this developmental stage. Additionally, AC6, PDE4B, and AKAP(1/2/8/9/12/13, and EZR) showed persistently high expression during the entire lung-developmental process, which provides a reference for the development and utilization of key gene subtypes in this pathway.

scholarly journals Mot3, a Zn Finger Transcription Factor That Modulates Gene Expression and Attenuates Mating Pheromone Signaling in Saccharomyces cerevisiae

Genetics ◽  
1998 ◽  
Vol 149 (2) ◽  
pp. 879-892 ◽  
Author(s):  
Anatoly V Grishin ◽  
Michael Rothenberg ◽  
Maureen A Downs ◽  
Kendall J Blumer
Keyword(s):  
Gene Expression ◽  
Saccharomyces Cerevisiae ◽  
Signaling Pathway ◽  
G Protein ◽  
Binding Sites ◽  
Dependent Manner ◽  
Pheromone Response ◽  
Mating Pheromone ◽  
Pheromone Signaling ◽  
Yeast Genes

Abstract In the yeast Saccharomyces cerevisiae, mating pheromone response is initiated by activation of a G protein- and mitogen-activated protein (MAP) kinase-dependent signaling pathway and attenuated by several mechanisms that promote adaptation or desensitization. To identify genes whose products negatively regulate pheromone signaling, we screened for mutations that suppress the hyperadaptive phenotype of wild-type cells overexpressing signaling-defective G protein β subunits. This identified recessive mutations in MOT3, which encodes a nuclear protein with two Cys2-His2 Zn fingers. MOT3 was found to be a dosage-dependent inhibitor of pheromone response and pheromone-induced gene expression and to require an intact signaling pathway to exert its effects. Several results suggested that Mot3 attenuates expression of pheromone-responsive genes by mechanisms distinct from those used by the negative transcriptional regulators Cdc36, Cdc39, and Mot2. First, a Mot3-lexA fusion functions as a transcriptional activator. Second, Mot3 is a dose-dependent activator of several genes unrelated to pheromone response, including CYC1, SUC2, and LEU2. Third, insertion of consensus Mot3 binding sites (C/A/T)AGG(T/C)A activates a promoter in a MOT3-dependent manner. These findings, and the fact that consensus binding sites are found in the 5′ flanking regions of many yeast genes, suggest that Mot3 is a globally acting transcriptional regulator. We hypothesize that Mot3 regulates expression of factors that attenuate signaling by the pheromone response pathway.

scholarly journals Molecular Rewiring of the Jasmonate Signaling Pathway to Control Auxin-Responsive Gene Expression

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 641
Author(s):  
Ning Li ◽  
Linggai Cao ◽  
Wenzhuo Miu ◽  
Ruibin Cao ◽  
Mingbo Peng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathway ◽  
Developmental Process ◽  
Expression System ◽  
Transient Gene Expression ◽  
Transcriptional Repressor ◽  
Auxin Signaling ◽  
General Strategy ◽  
Auxin Signaling Pathway ◽  
Responsive Gene

The plant hormone jasmonic acid (JA) has an important role in many aspects of plant defense response and developmental process. JA triggers interaction between the F-box protein COI1 and the transcriptional repressors of the JAZ family that leads the later to proteasomal degradation. The Jas-motif of JAZs is critical for mediating the COI1 and JAZs interaction in the presence of JA. Here, by using the protoplast transient gene expression system we reported that the Jas-motif of JAZ1 was necessary and sufficient to target a foreign reporter protein for COI1-facilitated degradation. We fused the Jas-motif to the SHY2 transcriptional repressor of auxin signaling pathway to create a chimeric protein JaSHY. Interestingly, JaSHY retained the transcriptional repressor function while become degradable by the JA coreceptor COI1 in a JA-dependent fashion. Moreover, the JA-induced and COI1-facilitated degradation of JaSHY led to activation of a synthetic auxin-responsive promoter activity. These results showed that the modular components of JA signal transduction pathway can be artificially redirected to regulate auxin signaling pathway and control auxin-responsive gene expression. Our work provides a general strategy for using synthetic biology approaches to explore and design cell signaling networks to generate new cellular functions in plant systems.

scholarly journals Conformational changes in the G protein Gs induced by the β2 adrenergic receptor

Nature ◽  
2011 ◽  
Vol 477 (7366) ◽  
pp. 611-615 ◽  
Author(s):  
Ka Young Chung ◽  
Søren G. F. Rasmussen ◽  
Tong Liu ◽  
Sheng Li ◽  
Brian T. DeVree ◽  
...  
Keyword(s):  
G Protein ◽  
Conformational Changes ◽  
Adrenergic Receptor ◽  
Β2 Adrenergic Receptor

Members of the G Protein-Coupled Receptor Kinase Family That Phosphorylate the β2-Adrenergic Receptor Facilitate Sequestration†

Biochemistry ◽  
1996 ◽  
Vol 35 (13) ◽  
pp. 4155-4160 ◽  
Author(s):  
Luc Ménard ◽  
Stephen S. G. Ferguson ◽  
Larry S. Barak ◽  
Lucie Bertrand ◽  
Richard T. Premont ◽  
...  
Keyword(s):  
G Protein ◽  
Adrenergic Receptor ◽  
Receptor Kinase ◽  
G Protein Coupled Receptor ◽  
Kinase Family ◽  
Β2 Adrenergic Receptor ◽  
G Protein Coupled

scholarly journals Targeted transgenesis identifies Gαs as the bottleneck in β2-adrenergic receptor cell signaling and physiological function in airway smooth muscle

2014 ◽  
Vol 307 (10) ◽  
pp. L775-L780 ◽  
Author(s):  
Wayne C. H. Wang ◽  
Susan H. Pauer ◽  
Dan'elle C. Smith ◽  
Madison A. Dixon ◽  
David J. Disimile ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Transgenic Mice ◽  
G Protein ◽  
Airway Smooth Muscle ◽  
Adrenergic Receptor ◽  
Coupling Efficiency ◽  
The Body ◽  
Limiting Factor ◽  
Camp Production ◽  
Β2 Adrenergic Receptor

G protein-coupled receptors are the most pervasive signaling superfamily in the body and act as receptors to endogenous agonists and drugs. For β-agonist-mediated bronchodilation, the receptor-G protein-effector network consists of the β2-adrenergic receptor (β2AR), Gs, and adenylyl cyclase, expressed on airway smooth muscle (ASM). Using ASM-targeted transgenesis, we previously explored which of these three early signaling elements represents a limiting factor, or bottleneck, in transmission of the signal from agonist binding to ASM relaxation. Here we overexpressed Gαs in transgenic mice and found that agonist-promoted relaxation of airways was enhanced in direct proportion to the level of Gαs expression. Contraction of ASM from acetylcholine was not affected in Gαs transgenic mice, nor was relaxation by bitter taste receptors. Furthermore, agonist-promoted (but not basal) cAMP production in ASM cells from Gαs-transgenic mice was enhanced compared with ASM from nontransgenic littermates. Agonist-promoted inhibition of platelet-derived growth factor-stimulated ASM proliferation was also enhanced in Gαs mouse ASM. The enhanced maximal β-agonist response was of similar magnitude for relaxation, cAMP production, and growth inhibition. Taken together, it appears that a limiting factor in β-agonist responsiveness in ASM is the expression level of Gαs. Gene therapy or pharmacological means of increasing Gαs (or its coupling efficiency to β2AR) thus represent an interface for development of novel therapeutic agents for improvement of β-agonist therapy.

Porcine hepatic response to sepsis and its amplification by an adrenergic receptor α1 agonist and a β2 antagonist

1998 ◽  
Vol 95 (4) ◽  
pp. 467-478 ◽  
Author(s):  
D. TIGHE ◽  
R. MOSS ◽  
D. BENNETT
Keyword(s):  
Inflammatory Response ◽  
G Protein ◽  
Protein Complex ◽  
Adrenergic Receptor ◽  
Receptor Agonist ◽  
Cell Surface Receptor ◽  
Ultrastructural Changes ◽  
Β2 Adrenergic Receptor ◽  
Adrenergic Receptor Agonist ◽  
Septic Group

1.We investigated the effect of adrenergic receptor stimulation or inhibition on the hepatic ultrastructural changes in a porcine faecal peritonitis model of multi-organ failure. We infused either the α1 adrenergic receptor agonist methoxamine or the β2 adrenergic receptor antagonist ICI 118551 during 8 ;h of the study. 2.Anaesthetized pigs (25–30 ;kg) were divided into four non-septic groups (control, non-septic, non-septic methoxamine and non-septic ICI 118551) and three septic groups (septic, septic methoxamine and septic ICI 118551). 3.Changes in hepatic ultrastructure were measured by morphometric analysis. The septic group was significantly worse than all the non-septic groups. Septic methoxamine and septic ICI 118551 were significantly worse than the septic group. 4.Septic methoxamine and septic ICI 118551 had a significantly increased perisinusoidal space; septic methoxamine had significant hepatocyte vacuolation. 5.Hepatic ultrastructural changes were independent of hepatic blood flow. 6.Septic methoxamine had significant myocardial depression. 7.The α1 adrenergic receptor agonist methoxamine or the β2 antagonist ICI 118551 both amplified the hepatic injury normally found during sepsis in our porcine model. 8.These findings suggest that during sepsis a protective endogenous β2 adrenergic receptor-mediated anti-inflammatory response is activated via cell membrane transduction to stimulate the trimeric G-protein complex Gs and activate the second cell messenger cAMP. 9.In addition, it is likely that α1 adrenergic receptor agonists amplify the inflammatory response by stimulating the cell-surface receptor-linked trimeric G-protein complex to activate Gq and the second cell messenger phospholipase C.

scholarly journals Receptor-Mediated Adenylyl Cyclase Activation Through XLαs, the Extra-Large Variant of the Stimulatory G Protein α-Subunit

2002 ◽  
Vol 16 (8) ◽  
pp. 1912-1919 ◽  
Author(s):  
Murat Bastepe ◽  
Yasemin Gunes ◽  
Beatriz Perez-Villamil ◽  
Joy Hunzelman ◽  
Lee S. Weinstein ◽  
...  
Keyword(s):  
Adenylyl Cyclase ◽  
G Protein ◽  
Adrenergic Receptor ◽  
Α Subunit ◽  
Exon 2 ◽  
Amino Terminal ◽  
Stimulatory G Protein ◽  
Β2 Adrenergic Receptor ◽  
Carboxyl Terminal ◽  
G Protein Α Subunit

Abstract XLαs, the large variant of the stimulatory G protein α subunit (Gsα), is derived from GNAS1 through the use of an alternative first exon and promoter. Gsα and XLαs have distinct amino-terminal domains, but are identical over the carboxyl-terminal portion encoded by exons 2–13. XLαs can mimic some functions of Gsα, including βγ interaction and adenylyl cyclase stimulation. However, previous attempts to demonstrate coupling of XLαs to typically Gs-coupled receptors have not been successful. We now report the generation of murine cell lines that carry homozygous disruption of Gnas exon 2, and are therefore null for endogenous XLαs and Gsα (GnasE2−/E2−). GnasE2−/E2− cells transfected with plasmids encoding XLαs and different heptahelical receptors, including the β2-adrenergic receptor and receptors for PTH, TSH, and CRF, showed agonist-mediated cAMP accumulation that was indistinguishable from that observed with cells transiently coexpressing Gsα and these receptors. Our findings thus indicate that XLαs is capable of functionally coupling to receptors that normally act via Gsα.

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