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

Citation
T. Kawaguchi et al., Glucose and cAMP regulate the L-type pyruvate kinase gene by phosphorylation/dephosphorylation of the carbohydrate response element binding protein, P NAS US, 98(24), 2001, pp. 13710-13715
Citations number
12
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN journal
00278424 → ACNP
Volume
98
Issue
24
Year of publication
2001
Pages
13710 - 13715
Database
ISI
SICI code
0027-8424(20011120)98:24<13710:GACRTL>2.0.ZU;2-3
Abstract
Recently we purified and identified a previously uncharacterized transcript ion 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 ge ne 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 (fi) 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, glu cose activated the nuclear import by dephosphorylation of Ser(196) in the c ytoplasm and also stimulated the DNA-binding activity by dephosphorylation of Thr(666) in the nucleus. These results thus reveal mechanisms for regula tion of ChREBP and the L-PK transcription by excess carbohydrate and cAMP.