Rapid activation of glycogen phosphorylase by the endoplasmic reticulum unfolded protein response

Arvind Gill, Ningguo Gao, Mark A. Lehrman

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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 posttranslational 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.

Original languageEnglish (US)
Pages (from-to)44747-44753
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number47
DOIs
StatePublished - Nov 22 2002

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Glycogen Phosphorylase
Unfolded Protein Response
Endoplasmic Reticulum
Chemical activation
Endoplasmic Reticulum Stress
Proteins
Hexoses
Glycosylation
Metabolism
Protein Unfolding
Enzyme Inhibitors
Adenosine Monophosphate
Cell Extracts
Glycogen
Phosphoric Monoester Hydrolases
Polysaccharides
Phosphorylation
Fibroblasts
Phosphates
Enzymes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Rapid activation of glycogen phosphorylase by the endoplasmic reticulum unfolded protein response. / Gill, Arvind; Gao, Ningguo; Lehrman, Mark A.

In: Journal of Biological Chemistry, Vol. 277, No. 47, 22.11.2002, p. 44747-44753.

Research output: Contribution to journalArticle

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