ArticleCell reports2025
P-Rex1 limits the agonist-induced internalization of GPCRs independently of its Rac-GEF activity.
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.
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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.
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Who cites it
4 citing papers in PubMed.
- Decoding the S1P-S1PR axis in cancer: Mechanisms, pathways and therapeutic horizons (Review).Biomedical reports · 2026Review
- Pan-cancer signaling landscape linked to endothelial and immune Sphingosine-1-phosphate receptor 1 (S1PR1) expression.In silico pharmacology · 2026Article
- P-Rex2 suppresses glucose uptake into liver and skeletal muscle through different adaptor functions.Scientific reports · 2025Article
- P-Rex1 controls phagocytosis and the killing of bacteria by murine neutrophils independently of its catalytic activity.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
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