ArticleCell chemical biology2022
Phosphorylation of guanosine monophosphate reductase triggers a GTP-dependent switch from pro- to anti-oncogenic function of EPHA4.
Article in Cell chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- GTP biosynthesis is a therapeutic vulnerability in Rac1-mutant melanoma.bioRxiv : the preprint server for biology · 2026Article
- SERINC2-mediated phosphatidylserine remodeling activates protrusion-localized AXL signaling to promote brain metastasis.Cell reports · 2026Article
- Integrated multi-omics reveals coordinatedmSystems · 2026Article
- Decoding Rho GTPase signalling networks in directed cell migration.Frontiers in cell and developmental biology · 2026Review
- Inhibitors of De Novo Guanylate Biosynthesis Enhance the Potency of MAPK Cascade Inhibitors Against Colorectal Cancer.International journal of molecular sciences · 2025Article
- Eph receptor tyrosine kinases are functional entry receptors for murine gammaherpesvirus 68.PLoS pathogens · 2025Article
- Article
- Eph receptors and ephrins in cancer progression.Nature reviews. Cancer · 2024Review
- Lipidation and PEGylation Strategies to Prolong theEuropean journal of medicinal chemistry · 2023Article
- Leveraging a disulfidptosis/ferroptosis-based signature to predict the prognosis of lung adenocarcinoma.Cancer cell international · 2023Article
- Compartmentalization and regulation of GTP in control of cellular phenotypes.Trends in molecular medicine · 2022Review
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Authors and funding
28 authors at 7 institutions in 1 country.
Funding
Abstract
Signal transduction pathways post-translationally regulating nucleotide metabolism remain largely unknown. Guanosine monophosphate reductase (GMPR) is a nucleotide metabolism enzyme that decreases GTP pools by converting GMP to IMP. We observed that phosphorylation of GMPR at Tyr267 is critical for its activity and found that this phosphorylation by ephrin receptor tyrosine kinase EPHA4 decreases GTP pools in cell protrusions and levels of GTP-bound RAC1. EPHs possess oncogenic and tumor-suppressor activities, although the mechanisms underlying switches between these two modes are poorly understood. We demonstrated that GMPR plays a key role in EPHA4-mediated RAC1 suppression. This supersedes GMPR-independent activation of RAC1 by EPHA4, resulting in a negative overall effect on melanoma cell invasion and tumorigenicity. Accordingly, EPHA4 levels increase during melanoma progression and inversely correlate with GMPR levels in individual melanoma tumors. Therefore, phosphorylation of GMPR at Tyr267 is a metabolic signal transduction switch controlling GTP biosynthesis and transformed phenotypes.
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Registered trials
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