ArticleNature communications2021
Protein kinase A controls the hexosamine pathway by tuning the feedback inhibition of GFAT-1.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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.
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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
23 citing papers in PubMed, 33 citations in OpenAlex.
- Hexosamine Biosynthetic Pathway and Fatty Acid β-Oxidative Imbalance: A Key Mechanism by Which Abnormal Macrophage Lipophagy Promotes Atherosclerosis in Diabetes.Cardiovascular drugs and therapy · 2026Review
- Decoding the Hexosamine Biosynthesis Pathway: Implications for Novel Therapeutic Strategies in Sarcoma.Journal of cellular physiology · 2026Review
- Developmentally-regulated post-apocrine cell death ofFrontiers in cell and developmental biology · 2026Article
- Genome-wide RNAi screening in C. elegans reveals OXPHOS and pyrimidine synthesis pathways as PKA regulators.Communications biology · 2025Article
- Exploring the metabolic signaling network of GFPT in cancer.Cell death discovery · 2025Review
- Metabolic syndrome in colorectal cancer liver metastasis: metabolic reprogramming and microenvironment crosstalk.Frontiers in immunology · 2025Review
- Food for thought: Nutrient metabolism controlling early T cell development.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- The post-translational modification O-GlcNAc is a sensor and regulator of metabolism.Open biology · 2024Review
- O-GlcNAcylation mediates Wnt-stimulated bone formation by rewiring aerobic glycolysis.EMBO reports · 2024Article
- Regulation of protein O-GlcNAcylation by circadian, metabolic, and cellular signals.The Journal of biological chemistry · 2024Review
- O-GlcNAcylation in ischemic diseases.Frontiers in pharmacology · 2024Review
- Review
- The UDPase ENTPD5 regulates ER stress-associated renal injury by mediating protein N-glycosylation.Cell death & disease · 2023Article
- Roles ofFrontiers in physiology · 2023Article
- Inhibitors of glucosamine-6-phosphate synthase as potential antimicrobials or antidiabetics - synthesis and properties.Journal of enzyme inhibition and medicinal chemistry · 2022Article
- Hexosamine pathway activation improves memory but does not extend lifespan in mice.Aging cell · 2022Article
- Nutrient-sensitive protein O-GlcNAcylation shapes daily biological rhythms.Open biology · 2022Review
- Mechanisms of coordinating hyaluronan and glycosaminoglycan production by nucleotide sugars.American journal of physiology. Cell physiology · 2022Review
- Review
- GFAT1 is highly expressed in cancer stem cells of pancreatic cancer.Annals of translational medicine · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hexosamine pathway (HP) is a key anabolic pathway whose product uridine 5'-diphospho-N-acetyl-D-glucosamine (UDP-GlcNAc) is an essential precursor for glycosylation processes in mammals. It modulates the ER stress response and HP activation extends lifespan in Caenorhabditis elegans. The highly conserved glutamine fructose-6-phosphate amidotransferase 1 (GFAT-1) is the rate-limiting HP enzyme. GFAT-1 activity is modulated by UDP-GlcNAc feedback inhibition and via phosphorylation by protein kinase A (PKA). Molecular consequences of GFAT-1 phosphorylation, however, remain poorly understood. Here, we identify the GFAT-1 R203H substitution that elevates UDP-GlcNAc levels in C. elegans. In human GFAT-1, the R203H substitution interferes with UDP-GlcNAc inhibition and with PKA-mediated Ser205 phosphorylation. Our data indicate that phosphorylation affects the interactions of the two GFAT-1 domains to control catalytic activity. Notably, Ser205 phosphorylation has two discernible effects: it lowers baseline GFAT-1 activity and abolishes UDP-GlcNAc feedback inhibition. PKA controls the HP by uncoupling the metabolic feedback loop of GFAT-1.
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Registered trials
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.