PMID- 14612449
OWN - NLM
STAT- MEDLINE
DCOM- 20040423
LR  - 20211203
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 279
IP  - 4
DP  - 2004 Jan 23
TI  - The transcription factors HIF-1 and HNF-4 and the coactivator p300 are involved 
      in insulin-regulated glucokinase gene expression via the phosphatidylinositol 
      3-kinase/protein kinase B pathway.
PG  - 2623-31
AB  - Glucokinase plays a key role in the regulation of glucose utilization in liver 
      and its expression is strongly enhanced by insulin and modulated by venous pO(2). 
      In primary rat hepatocytes, pO(2) modulated insulin-dependent glucokinase (GK) 
      gene expression was abolished by wortmannin an inhibitor of phosphatidylinositol 
      3-kinase (PI3K). Transfection of vectors encoding the p110 catalytic subunit of 
      PI3K or constitutively active protein kinase B (PKB) stimulated GK mRNA and 
      protein expression. The transfection of GK promoter constructs together with 
      expression vectors for p110 or constitutively active PKB revealed that the GK 
      promoter region -87/-80 mediates the response to PI3K/PKB. Transfection 
      experiments and gel shift assays show that this element is able to bind 
      hypoxia-inducible factor-1 (HIF-1) in a hypoxia- and PKB-dependent manner. The 
      ability of HIF-1alpha to activate the GK promoter was enhanced by hepatocyte 
      nuclear factor-4alpha (HNF-4alpha), acting via the sequence -52/-39, and by the 
      coactivator p300. Stimulation of the GK promoter by insulin was dependent on the 
      intact -87/-80 region and maximal stimulation was achieved when HIF-1alpha, 
      HNF-4, and p300 were cotransfected with the -1430 GK promoter Luc construct in 
      primary hepatocytes. Maximal stimulation of GK promoter activity by insulin was 
      inhibited when a p300 vector was used containing a mutation within a PKB 
      phosphorylation site. Thus, a regulatory transcriptional complex consisting of 
      HIF-1, HNF-4, and p300 appears to be involved in insulin-dependent GK gene 
      activation.
FAU - Roth, Ulrike
AU  - Roth U
AD  - Institut fur Biochemie und Molekulare Zellbiologie, Georg-August-Universitat, 
      Humboldtallee 23, D-37073 Gottingen, Germany.
FAU - Curth, Katja
AU  - Curth K
FAU - Unterman, Terry G
AU  - Unterman TG
FAU - Kietzmann, Thomas
AU  - Kietzmann T
LA  - eng
GR  - DKK1430/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20031110
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Hepatocyte Nuclear Factor 4)
RN  - 0 (Hif1a protein, rat)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Insulin)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - EC 2.3.1.48 (Histone Acetyltransferases)
RN  - EC 2.3.1.48 (Nuclear Receptor Coactivator 3)
RN  - EC 2.7.1.2 (Glucokinase)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - DNA-Binding Proteins/*metabolism
MH  - Enzyme Induction/genetics
MH  - Gene Expression Regulation, Enzymologic
MH  - Glucokinase/*biosynthesis/genetics
MH  - Hepatocyte Nuclear Factor 4
MH  - Histone Acetyltransferases
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Insulin/metabolism
MH  - Liver/*enzymology
MH  - Male
MH  - Nuclear Proteins/*metabolism
MH  - Nuclear Receptor Coactivator 3
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphoproteins/*metabolism
MH  - *Protein Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Rats
MH  - Rats, Wistar
MH  - Signal Transduction/genetics
MH  - Trans-Activators/*metabolism
MH  - Transcription Factors/*metabolism
MH  - Transcriptional Activation
EDAT- 2003/11/13 05:00
MHDA- 2004/04/24 05:00
CRDT- 2003/11/13 05:00
PHST- 2003/11/13 05:00 [pubmed]
PHST- 2004/04/24 05:00 [medline]
PHST- 2003/11/13 05:00 [entrez]
AID - S0021-9258(18)52628-4 [pii]
AID - 10.1074/jbc.M308391200 [doi]
PST - ppublish
SO  - J Biol Chem. 2004 Jan 23;279(4):2623-31. doi: 10.1074/jbc.M308391200. Epub 2003 
      Nov 10.