PMID- 15367685
OWN - NLM
STAT- MEDLINE
DCOM- 20041101
LR  - 20181113
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 24
IP  - 19
DP  - 2004 Oct
TI  - Phosphorylation of C/EBPbeta at a consensus extracellular signal-regulated 
      kinase/glycogen synthase kinase 3 site is required for the induction of 
      adiponectin gene expression during the differentiation of mouse fibroblasts into 
      adipocytes.
PG  - 8671-80
AB  - Stimulation of adipogenesis in mouse preadipocytes requires C/EBPbeta as well as 
      activation of the MEK/extracellular signal-regulated kinase (ERK) signaling 
      pathway. In this study, we demonstrate that phosphorylation of C/EBPbeta at a 
      consensus ERK/glycogen synthase kinase 3 (GSK3) site regulates adiponectin gene 
      expression during the C/EBPbeta-facilitated differentiation of mouse fibroblasts 
      into adipocytes. First, we show that exposure of 3T3-L1 preadipocytes to insulin, 
      dexamethasone (DEX), and isobutylmethylxanthine (MIX) leads to the 
      phosphorylation of C/EBPbeta at threonine 188. Pretreating the cells with a 
      MEK1-specific inhibitor (U0126) significantly attenuates this activity. 
      Similarly, these effectors activate the phosphorylation of T188 within an ectopic 
      C/EBPbeta overexpressed in Swiss mouse fibroblasts, and this event involves both 
      MEK1 and GSK3 activity. We further show that expression of C/EBPbeta (p34kD LAP 
      isoform) in Swiss mouse fibroblasts exposed to DEX, MIX, and insulin induces 
      expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and 
      some adiponectin but that it does not activate expression of FABP4/aP2. In fact, 
      complete conversion of these fibroblasts into lipid-laden adipocytes, which 
      includes activation of FABP4 and adiponectin expression, requires their exposure 
      to a potent PPARgamma ligand such as troglitazone. Expression of a mutant 
      C/EBPbeta in which threonine 188 has been modified to alanine (C/EBPbeta T188A) 
      can induce PPARgamma production in the mouse fibroblasts, but it is incapable of 
      stimulating adiponectin expression in the absence or presence of troglitazone. 
      Interestingly, replacement of T188 with aspartic acid creates a C/EBPbeta 
      molecule (C/EBPbeta T188D) that possesses adipogenic activity similar to that of 
      the wild-type molecule. The absence of adiponectin expression correlates with a 
      reduced amount of C/EBPalpha in the adipocytes expressing the T188A mutant 
      suggesting that C/EBPalpha is required for expression of adiponectin. In fact, 
      ectopic expression of PPARgamma in C/EBPalpha-deficient fibroblasts (NIH 3T3 
      cells) produces a modest amount of adiponectin, whereas expression of both 
      PPARgamma and C/EBPalpha in NIH 3T3 cells facilitates production of abundant 
      quantities of adiponectin. These data demonstrate that phosphorylation of 
      C/EBPbeta at a consensus ERK/GSK3 site is required for both C/EBPalpha and 
      adiponectin gene expression during the differentiation of mouse fibroblasts into 
      adipocytes.
FAU - Park, Bae-Hang
AU  - Park BH
AD  - Department of Biochemistry, Boston University School of Medicine, 715 Albany St., 
      Boston, MA 02118, USA.
FAU - Qiang, Li
AU  - Qiang L
FAU - Farmer, Stephen R
AU  - Farmer SR
LA  - eng
GR  - R56 DK051586/DK/NIDDK NIH HHS/United States
GR  - R01 DK051586/DK/NIDDK NIH HHS/United States
GR  - R01 DK058825/DK/NIDDK NIH HHS/United States
GR  - DK58825/DK/NIDDK NIH HHS/United States
GR  - DK51586/DK/NIDDK NIH HHS/United States
GR  - R56 DK058825/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Adiponectin)
RN  - 0 (CCAAT-Enhancer-Binding Protein-beta)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Proteins)
RN  - 2ZD004190S (Threonine)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Adipocytes/*cytology
MH  - Adiponectin
MH  - Animals
MH  - CCAAT-Enhancer-Binding Protein-beta/genetics/*metabolism
MH  - Cell Differentiation/*physiology
MH  - Fibroblasts/cytology
MH  - Gene Expression Regulation/physiology
MH  - Glycogen Synthase Kinase 3/metabolism
MH  - *Intercellular Signaling Peptides and Proteins
MH  - Lipid Metabolism
MH  - Mice
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Mutation
MH  - Phosphorylation
MH  - Proteins/*metabolism
MH  - Threonine/metabolism
PMC - PMC516726
EDAT- 2004/09/16 05:00
MHDA- 2004/11/02 09:00
PMCR- 2004/10/01
CRDT- 2004/09/16 05:00
PHST- 2004/09/16 05:00 [pubmed]
PHST- 2004/11/02 09:00 [medline]
PHST- 2004/09/16 05:00 [entrez]
PHST- 2004/10/01 00:00 [pmc-release]
AID - 24/19/8671 [pii]
AID - 0136-04 [pii]
AID - 10.1128/MCB.24.19.8671-8680.2004 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2004 Oct;24(19):8671-80. doi: 10.1128/MCB.24.19.8671-8680.2004.