The intersections betweenO-GlcNAcylation and phosphorylation: implications for multiple signaling pathways
Open Access
- 1 January 2010
- journal article
- review article
- Published by The Company of Biologists in Journal of Cell Science
- Vol. 123 (1), 13-22
- https://doi.org/10.1242/jcs.053678
Abstract
A paradigm-changing discovery in biology came about when it was found that nuclear and cytosolic proteins could be dynamically glycosylated with a single O-linked β-N-acetylglucosamine (O-GlcNAc) moiety. O-GlcNAcylation is akin to phosphorylation: it occurs on serine and/or threonine side chains of proteins, and cycles rapidly upon cellular activation. O-GlcNAc and phosphate show a complex interplay: they can either competitively occupy a single site or proximal sites, or noncompetitively occupy different sites on a substrate. Phosphorylation regulates O-GlcNAc-cycling enzymes and, conversely, O-GlcNAcylation controls phosphate-cycling enzymes. Such crosstalk is evident in all compartments of the cell, a finding that is congruent with the fundamental role of O-GlcNAc in regulating nutrient- and stress-induced signal transduction. O-GlcNAc transferase is recruited to the plasma membrane in response to insulin and is targeted to substrates by forming transient holoenzyme complexes that have different specificities. Cytosolic O-GlcNAcylation is important for the proper transduction of signaling cascades such as the NFκB pathway, whereas nuclear O-GlcNAc is crucial for regulating the activity of numerous transcription factors. This Commentary focuses on recent findings supporting an emerging concept that continuous crosstalk between phosphorylation and O-GlcNAcylation is essential for the control of vital cellular processes and for understanding the mechanisms that underlie certain neuropathologies.Keywords
This publication has 89 references indexed in Scilit:
- Drosophila O -GlcNAc transferase (OGT) is encoded by the Polycomb group (PcG) gene, super sex combs ( sxc )Proceedings of the National Academy of Sciences of the United States of America, 2009
- Regulation of Calcium/Calmodulin-dependent Kinase IV by O-GlcNAc ModificationOnline Journal of Public Health Informatics, 2009
- O-Linked N-Acetylglucosamine Modification on CCAAT Enhancer-binding Protein βOnline Journal of Public Health Informatics, 2009
- Identification of protein O-GlcNAcylation sites using electron transfer dissociation mass spectrometry on native peptidesProceedings of the National Academy of Sciences of the United States of America, 2009
- Loss of p53 enhances catalytic activity of IKKβ through O-linked β-N-acetyl glucosamine modificationProceedings of the National Academy of Sciences of the United States of America, 2009
- Elevation of Global O-GlcNAc Levels in 3T3-L1 Adipocytes by Selective Inhibition of O-GlcNAcase Does Not Induce Insulin ResistanceOnline Journal of Public Health Informatics, 2008
- Axonal transport and the delivery of pre-synaptic componentsCurrent Opinion in Neurobiology, 2008
- Regulation of the O-Linked β-N-Acetylglucosamine Transferase by Insulin SignalingOnline Journal of Public Health Informatics, 2008
- AMP-activated Protein Kinase and p38 MAPK Activate O-GlcNAcylation of Neuronal Proteins during Glucose DeprivationJournal of Biological Chemistry, 2008
- Caenorhabditis elegans ortholog of a diabetes susceptibility locus: oga-1 ( O -GlcNAcase) knockout impacts O -GlcNAc cycling, metabolism, and dauerProceedings of the National Academy of Sciences of the United States of America, 2006