Evidence map›Paper›PMID 41100251›Full record

ArticleCell reports2025

P-Rex1 limits the agonist-induced internalization of GPCRs independently of its Rac-GEF activity.

Martin J Baker, Elizabeth Hampson, Priota Islam, Ruben Pelaez Moral, Eve A Maunders, Kirsti Hornigold, Elpida Tsonou, Angeliki Malliri, David C Hornigold, Roderick E Hubbard and 2 more

Abstract read
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. 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

12 authors.

Martin J BakerSignalling Programme, The Babraham Institute, Babraham Research Campus, Cambridge, UK; Cell Signalling Group, Cancer Research UK Manchester Institute, University of Manchester, Wilmslow Road, Manchester, UK.
Elizabeth HampsonSignalling Programme, The Babraham Institute, Babraham Research Campus, Cambridge, UK.
Priota IslamSignalling Programme, The Babraham Institute, Babraham Research Campus, Cambridge, UK.
Ruben Pelaez MoralSignalling Programme, The Babraham Institute, Babraham Research Campus, Cambridge, UK.
Eve A MaundersSignalling Programme, The Babraham Institute, Babraham Research Campus, Cambridge, UK.
Kirsti HornigoldSignalling Programme, The Babraham Institute, Babraham Research Campus, Cambridge, UK.
Elpida TsonouSignalling Programme, The Babraham Institute, Babraham Research Campus, Cambridge, UK; Bioscience Metabolism, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Angeliki MalliriCell Signalling Group, Cancer Research UK Manchester Institute, University of Manchester, Wilmslow Road, Manchester, UK.
David C HornigoldBioscience Metabolism, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Roderick E HubbardVernalis (R&D) Ltd., Granta Park, Cambridge, UK.
Andrew J MasseyVernalis (R&D) Ltd., Granta Park, Cambridge, UK.
Heidi C E WelchSignalling Programme, The Babraham Institute, Babraham Research Campus, Cambridge, UK. Electronic address: heidi.welch@babraham.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The guanine-nucleotide exchange factor (GEF) P-Rex1 mediates G protein-coupled receptor (GPCR) signaling by activating the small GTPase Rac. We show here that P-Rex1 also controls GPCR trafficking. P-Rex1 inhibits the agonist-stimulated internalization of the GPCR S1PR1 independently of its Rac-GEF activity, through its PDZ, DEP, and inositol polyphosphate 4-phosphatase domains. P-Rex1 also limits the agonist-induced trafficking of CXCR4, PAR4, and GLP1R but does not control steady-state GPCR levels, nor the agonist-induced internalization of the receptor tyrosine kinases PDGFR and EGFR. P-Rex1 blocks the phosphorylation required for GPCR internalization. P-Rex1 binds G protein-coupled receptor kinase 2 (Grk2), both in vitro and in cells, but does not appear to regulate Grk2 activity. We propose that P-Rex1 limits the agonist-induced internalization of GPCRs through its interaction with Grk2 to maintain high levels of active GPCRs at the plasma membrane. Therefore, P-Rex1 plays a dual role in promoting GPCR responses by controlling GPCR trafficking through an adapter function as well as by mediating GPCR signaling through its Rac-GEF activity.

Indexed as

Guanine Nucleotide Exchange Factorsrac GTP-Binding ProteinsReceptors, G-Protein-CoupledAnimalsCell MembraneG-Protein-Coupled Receptor Kinase 2HEK293 CellsHumansPhosphorylationProtein TransportSignal TransductionSphingosine-1-Phosphate ReceptorsG-Protein-Coupled Receptor Kinase 2GRK2 protein, humanGuanine Nucleotide Exchange FactorsPREX1 protein, humanrac GTP-Binding ProteinsReceptors, G-Protein-CoupledSphingosine-1-Phosphate Receptorsagonist-induced internalizationCP: Molecular biologyGEFGPCRG protein-coupled receptorGRK2guanine-nucleotide exchange factorPREX1PREX2trafficking

Identifiers

PMID41100251
PMCPMC12569377

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.