Evidence map›Paper›PMID 18362331›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2008

Alternative splicing of the G protein-coupled receptor superfamily in human airway smooth muscle diversifies the complement of receptors.

Richard Einstein, Heather Jordan, Weiyin Zhou, Michael Brenner, Esther G Moses, Stephen B Liggett

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
3.3field-weighted citation impact, top 7% 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

43 citing papers in PubMed, 73 citations in OpenAlex.

  1. Molecular mechanism of bitter taste receptor agonist-mediated relaxation of airway smooth muscle.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024
    Article
  2. Article
  3. Review
  4. Article
  5. The future of bronchodilation: looking for new classes of bronchodilators.European respiratory review : an official journal of the European Respiratory Society · 2019
    Review
  6. Obesity-induced asthma: Role of free fatty acid receptors.The Japanese dental science review · 2019
    Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Vagal innervation is required for pulmonary function phenotype inAmerican journal of physiology. Lung cellular and molecular physiology · 2017
    Article
  12. Article
  13. Article
  14. Novel identification of the free fatty acid receptor FFAR1 that promotes contraction in airway smooth muscle.American journal of physiology. Lung cellular and molecular physiology · 2015
    Article
  15. Article
  16. Genetic variation in HTR4 and lung function: GWAS follow-up in mouse.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015
    Article
  17. Article
  18. Article
  19. Article
  20. Bitter taste receptor function in asthmatic and nonasthmatic human airway smooth muscle cells.American journal of respiratory cell and molecular biology · 2014
    Article
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

6 authors at 1 institution in 1 country.

Richard EinsteinExonHit Therapeutics, Inc., 217 Perry Parkway, Building 5, Gaithersburg, MD 20877, USA.
Heather Jordan
Weiyin Zhou
Michael Brenner
Esther G Moses
Stephen B Liggett
University of Maryland, Baltimore · US

Funding

THE PHARMACOGENETICS OF ASTHMA TREATMENTU01HL065899 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI TANTISIRA, KELAN G, WEISS, SCOTT T · 2000 to 2014
$38.5M
Basis of Variability of Lung GPCR SignalingR01HL071609 · NHLBI · UNIVERSITY OF SOUTH FLORIDA · PI LIGGETT, STEPHEN B · 2003 to 2013
$3.7M
NHLBI NIH HHS HL065899NHLBI NIH HHS HL071609NHLBI NIH HHS R01 HL071609NHLBI NIH HHS U01 HL065899
6 · The paper itself

Abstract

G protein-coupled receptors (GPCRs) are the largest signaling family in the genome, serve an expansive array of functions, and are targets for approximately 50% of current therapeutics. In many tissues, such as airway smooth muscle (ASM), complex, unexpected, or paradoxical responses to agonists/antagonists occur without known mechanisms. We hypothesized that ASM express many more GPCRs than predicted, and that these undergo substantial alternative splicing, creating a highly diversified receptor milieu. Transcript arrays were designed detecting 434 GPCRs and their predicted splice variants. In this cell type, 353 GPCRs were detected (including 111 orphans), with expression levels varying by approximately 900-fold. Receptors used for treating airway disease were expressed lower than others with similar signaling properties, indicating potentially more effective targets. A disproportionate number of Class-A peptide-group receptors, and those coupling to G(q)/(11) or G(s) (vs. G(i)), was found. Importantly, 192 GPCRs had, on average, five different expressed receptor isoforms because of splicing events, including alternative splice donors and acceptors, novel introns, intron retentions, exon(s) skips, and novel exons, with the latter two events being most prevalent. The consequences of splicing were further investigated with the leukotriene B4 receptor, known for its aberrant responsiveness in lung. We found transcript expression of three variants because of alternative donor and acceptor splice sites, representing in-frame deletions of 38 and 100 aa, with protein expression of all three isoforms. Thus, alternative splicing, subject to conditional, temporal, and cell-type regulation, is a major mechanism that diversifies the GPCR superfamily, creating local recepteromes with specialized environments.

Indexed as

Alternative SplicingAmino Acid SequenceGenome, HumanHumansMolecular Sequence DataMuscle, SmoothReceptors, G-Protein-CoupledRespiratory SystemTranscription, GeneticReceptors, G-Protein-Coupled

Identifiers

PMID18362331
PMCPMC2278184
OpenAlexW2165091334

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.