Rapid activation of glycogen phosphorylase by the endoplasmic reticulum unfolded protein response
| Autor: | Arvind Gill, Ningguo Gao, Mark A. Lehrman |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Cytoplasm
Protein Folding Glycosylation Phosphatase Glucose-6-Phosphate Biology Endoplasmic Reticulum Biochemistry chemistry.chemical_compound Glycogen phosphorylase Polysaccharides Caffeine Humans Hexosephosphates Molecular Biology Cells Cultured Glycogen Endoplasmic reticulum Tunicamycin Glycogen Phosphorylase Cell Biology Dermis Fibroblasts Adenosine Monophosphate Phosphoric Monoester Hydrolases Enzyme Activation Dithiothreitol chemistry Unfolded protein response Phosphorylation |
| Zdroj: | The Journal of biological chemistry. 277(47) |
| ISSN: | 0021-9258 |
| Popis: | Endoplasmic reticulum (ER) stress is associated with misfolding of ER proteins and triggers the unfolded protein response (UPR). The UPR, in turn, helps restore normal ER function. Since fastidious N-linked glycosylation is critical for folding of most ER proteins, this study examined whether metabolic interconversions of precursors used for glycan assembly were controlled by the UPR. Thus, eight enzymes and factors with key roles in hexose phosphate metabolism were assayed in cytoplasmic extracts from primary dermal fibroblasts treated with UPR inducers. Stimulation of only one activity by the UPR was detected, AMP-independent glycogen phosphorylase (GP). GP activation required only 20 min of ER stress, with concurrent decreases in cellular glycogen and elevations of its metabolites Glc-1-P and Glc-6-P. Addition of phosphatase inhibitors to enzyme extracts from unstressed cells mimicked the effect of ER stress on GP activity, suggesting that phosphorylation of GP or a regulatory factor was involved. These data show that the UPR can modulate hexose metabolism in a manner beneficial for protein glycosylation. Since activation of GP appears to occur by a rapid post-translational process, it may be part of a general strategy of ER damage control, preceding the well-known transcription-dependent processes of the UPR that are manifested hours after the occurrence of ER stress. |
| Databáze: | OpenAIRE |
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