Evidence map›Paper›PMID 25260754›Full record

ArticleAmerican journal of physiology. Lung cellular and molecular physiology2014

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

Wayne C H Wang, Susan H Pauer, Dan'elle C Smith, Madison A Dixon, David J Disimile, Alfredo Panebra, Steven S An, Blanca Camoretti-Mercado, Stephen B Liggett

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of physiology. Lung cellular and molecular physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.6field-weighted citation impact, top 32% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Article
  3. A functional SNP upstream of theInternational journal of chronic obstructive pulmonary disease · 2018
    Article
  4. Review
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Wayne C H WangDepartment of Medicine, University of Maryland School of Medicine, Baltimore, Maryland;
Susan H PauerDepartment of Medicine, University of South Florida Morsani College of Medicine, Tampa, Florida; Center for Personalized Medicine and Genomics, University of South Florida Morsani College of Medicine, Tampa, Florida;
Dan'elle C SmithDepartment of Medicine, University of South Florida Morsani College of Medicine, Tampa, Florida; Center for Personalized Medicine and Genomics, University of South Florida Morsani College of Medicine, Tampa, Florida;
Madison A DixonDepartment of Medicine, University of South Florida Morsani College of Medicine, Tampa, Florida; Center for Personalized Medicine and Genomics, University of South Florida Morsani College of Medicine, Tampa, Florida;
David J DisimileDepartment of Medicine, University of South Florida Morsani College of Medicine, Tampa, Florida; Center for Personalized Medicine and Genomics, University of South Florida Morsani College of Medicine, Tampa, Florida;
Alfredo PanebraDepartment of Medicine, University of Maryland School of Medicine, Baltimore, Maryland;
Steven S AnDepartment of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; and.
Blanca Camoretti-MercadoDepartment of Medicine, University of South Florida Morsani College of Medicine, Tampa, Florida; Center for Personalized Medicine and Genomics, University of South Florida Morsani College of Medicine, Tampa, Florida;
Stephen B LiggettDepartment of Medicine, University of South Florida Morsani College of Medicine, Tampa, Florida; Center for Personalized Medicine and Genomics, University of South Florida Morsani College of Medicine, Tampa, Florida; Department of Molecular Pharmacology and Physiology, University of South Florida Morsani College of Medicine, Tampa, Florida sliggett@health.usf.edu.
University of South Florida · USUniversity of Maryland, Baltimore · USJohns Hopkins University · US

Funding

Basis of Variability of Lung GPCR SignalingR01HL071609 · NHLBI · UNIVERSITY OF SOUTH FLORIDA · PI LIGGETT, STEPHEN B · 2003 to 2013
$3.7M
Molecular properties of B-adrenergic receptors in AsthmaR37HL045967 · NHLBI · UNIVERSITY OF SOUTH FLORIDA · PI LIGGETT, STEPHEN B · 2002 to 2012
$3.2M
Novel Mechanisms of Smooth Muscle Beta2-receptor Regulation Relevant to AsthmaR01HL104119 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI HASDAY, JEFFREY D · 2010 to 2014
$1.8M
MOLECULAR PROPERTIES OF B-ADRENERGIC RECEPTORS IN ASTHMAR01HL045967 · NHLBI · UNIVERSITY OF SOUTH FLORIDA · PI LIGGETT, STEPHEN B · 1990 to 2018
$1.3M
Molecular properties of B-adrenergic receptors in AsthmaR56HL045967 · NHLBI · UNIVERSITY OF SOUTH FLORIDA · PI LIGGETT, STEPHEN B · 2015 to 2015
$374k
NHLBI NIH HHS HL-045967NHLBI NIH HHS HL-071609NHLBI NIH HHS HL-104119NHLBI NIH HHS R01 HL045967NHLBI NIH HHS R01 HL071609NHLBI NIH HHS R01 HL104119NHLBI NIH HHS R37 HL045967NHLBI NIH HHS R56 HL045967
6 · The paper itself

Abstract

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.

Indexed as

Signal TransductionAdrenergic beta-2 Receptor AgonistsAnimalsBronchodilator AgentsCell LineGene Expression Regulation, EnzymologicGTP-Binding Protein alpha SubunitsMiceMice, TransgenicMuscle, SmoothReceptors, Adrenergic, beta-2Respiratory SystemAdrenergic beta-2 Receptor AgonistsBronchodilator AgentsGTP-Binding Protein alpha SubunitsReceptors, Adrenergic, beta-2bronchodilationrelaxationstoichiometryβ-agonist

Identifiers

PMID25260754
PMCPMC4233293
OpenAlexW2328810018

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.