Evidence map›Paper›PMID 27888281›Full record

ArticleNaunyn-Schmiedeberg's archives of pharmacology2017

The actions of relaxin family peptides on signal transduction pathways activated by the relaxin family peptide receptor RXFP4.

Sheng Y Ang, Dana S Hutchinson, Bronwyn A Evans, Mohammed A Hossain, Nitin Patil, Ross A D Bathgate, Martina Kocan, Roger J Summers

Abstract readComparative Study
PubMed Publisher
In one paragraph

Article in Naunyn-Schmiedeberg's archives of pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.2field-weighted citation impact, top 16% 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

6 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. 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

8 authors at 3 institutions in 1 country.

Sheng Y AngDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia.
Dana S HutchinsonDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia.
Bronwyn A EvansDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia.
Mohammed A HossainThe Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia.
Nitin PatilThe Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia.
Ross A D BathgateThe Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia.
Martina KocanThe Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia.
Roger J SummersDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia. roger.summers@monash.edu.
Monash University · AUFlorey Institute of Neuroscience and Mental Health · AUUniversity of Melbourne · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The relaxin family peptide receptor 4 (RXFP4) is a G protein-coupled receptor (GPCR) expressed in the colorectum with emerging roles in metabolism and appetite regulation. It is activated by its cognate ligand insulin-like peptide 5 (INSL5) that is expressed in enteroendocrine L cells in the gut. Whether other evolutionarily related peptides such as relaxin-2, relaxin-3, or INSL3 activate RXFP4 signal transduction mechanisms with a pattern similar to or distinct from INSL5 is still unclear. In this study, we compare the signaling pathways activated by various relaxin family peptides to INSL5. We found that, like INSL5, relaxin-3 activated ERK1/2, p38MAPK, Akt, and S6RP phosphorylations leading to increased cell proliferation and also caused GRK and β-arrestin-mediated receptor internalization. Interestingly, relaxin-3 was slightly more potent than INSL5 in ERK1/2 and Akt phosphorylations, but both peptides were almost equipotent in adenylyl cyclase inhibition, S6RP phosphorylation, and cell proliferation. In addition, relaxin-3 showed greater efficacy only in Akt phosphorylation but not in the other pathways investigated. In contrast, no signaling activity or receptor internalization mechanisms were observed following relaxin-2 and INSL3. In conclusion, relaxin-3 is a high-efficacy agonist at RXFP4 with a comparable signal transduction profile to INSL5.

Indexed as

Adenylyl CyclasesAnimalsbeta-ArrestinsCell ProliferationCHO CellsCricetulusDose-Response Relationship, DrugEnzyme ActivationExtracellular Signal-Regulated MAP KinasesG-Protein-Coupled Receptor Kinase 2HumansInsulinLigandsp38 Mitogen-Activated Protein KinasesPhosphorylationProteinsAdenylyl Cyclasesbeta-ArrestinsExtracellular Signal-Regulated MAP KinasesG-Protein-Coupled Receptor Kinase 2InsulinLeydig insulin-like proteinLigandsp38 Mitogen-Activated Protein KinasesProteinsProto-Oncogene Proteins c-aktReceptors, G-Protein-CoupledReceptors, PeptideRelaxinRibosomal Protein S6 KinasesRLN2 protein, humanRLN3 protein, humanRXFP4 protein, humanInsulin-like peptide 3Insulin-like peptide 5Relaxin-2Relaxin-3Relaxin family peptide receptor 4Signal transduction

Identifiers

PMID27888281
OpenAlexW2554723591

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.