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• W3156111352 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." @default.
• W3156111352 created "2021-04-26" @default.
• W3156111352 creator A5016637247 @default.
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• W3156111352 creator A5063376543 @default.
• W3156111352 creator A5072991808 @default.
• W3156111352 creator A5089776656 @default.
• W3156111352 date "2021-04-12" @default.
• W3156111352 modified "2023-10-01" @default.
• W3156111352 title "Protein kinase A controls the hexosamine pathway by tuning the feedback inhibition of GFAT-1" @default.
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• W3156111352 doi "https://doi.org/10.1038/s41467-021-22320-y" @default.
• W3156111352 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8041777" @default.
• W3156111352 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33846315" @default.
• W3156111352 hasPublicationYear "2021" @default.
• W3156111352 type Work @default.
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• W3156111352 crossrefType "journal-article" @default.
• W3156111352 hasAuthorship W3156111352A5016637247 @default.
• W3156111352 hasAuthorship W3156111352A5026335531 @default.
• W3156111352 hasAuthorship W3156111352A5063376543 @default.

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