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Glucose and cAMP regulate the L-type pyruvate kinase gene by phosphorylation/dephosphorylation of the carbohydrate response element binding protein

Open access
Kawaguchi, Takumi, Takenoshita, Makoto, Kabashima, Tsutomu, Uyeda, Kosaku·2001·Proceedings of the National Academy of Sciences

Abstract

Recently we purified and identified a previously uncharacterized transcription factor from rat liver binding to the carbohydrate responsive element of the L-type pyruvate kinase (L-PK) gene. This factor was named carbohydrate responsive element binding protein (ChREBP). ChREBP, essential for L-PK gene transcription, is activated by high glucose and inhibited by cAMP. Here, we demonstrated that ( i ) nuclear localization signal and basic helix-loop-helix/leucine-zipper domains of ChREBP were essential for the transcription, and ( ii ) these domains were the targets of regulation by cAMP and glucose. Among three cAMP-dependent protein kinase phosphorylation sites, Ser 196 and Thr 666 were the target sites. Phosphorylation of the former resulted in inactivation of nuclear import, and that of the latter resulted in loss of the DNA-binding activity and L-PK transcription. On the other hand, glucose activated the nuclear import by dephosphorylation of Ser 196 in the cytoplasm and also stimulated the DNA-binding activity by dephosphorylation of Thr 666 in the nucleus. These results thus reveal mechanisms for regulation of ChREBP and the L-PK transcription by excess carbohydrate and cAMP.

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Metadata

Authors
Kawaguchi, T., Takenoshita, M., Kabashima, T., & Uyeda, K.
Venue
Proceedings of the National Academy of Sciences
Published
2001-11-06
Volume
98
Issue
24
Pages
13710-13715
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2083819344
Cited by
373
References
10
FWCI
4.34
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Glucose and cAMP regulate the L-type pyruvate kinase gene by phosphorylation/dephosphorylation of the carbohydrate response element binding protein. https://app.cochat.ai/papers/10.1073/pnas.231370798
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Kawaguchi, T., Takenoshita, M., Kabashima, T., & Uyeda, K. (2001). Glucose and cAMP regulate the L-type pyruvate kinase gene by phosphorylation/dephosphorylation of the carbohydrate response element binding protein. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.231370798

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