PMID- 15837948
OWN - NLM
STAT- MEDLINE
DCOM- 20051115
LR  - 20211203
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 111
IP  - 15
DP  - 2005 Apr 19
TI  - Phosphorylation of GATA2 by Akt increases adipose tissue differentiation and 
      reduces adipose tissue-related inflammation: a novel pathway linking obesity to 
      atherosclerosis.
PG  - 1946-53
AB  - BACKGROUND: Obesity-related inflammation is emerging as a major cause of insulin 
      resistance and cardiovascular diseases. GATA2 transcription factor is an 
      inhibitor of adipogenesis and an activator of vascular cells. We hypothesized 
      that GATA2 activity is controlled by insulin during adipogenesis, linking 
      metabolic homeostasis and inflammation. METHODS AND RESULTS: We show that insulin 
      induces GATA2 phosphorylation on serine 401 in a PI-3K/Akt-dependent manner. 
      Insulin-dependent phosphorylation of serine 401 impairs GATA2 translocation to 
      the nucleus and its DNA binding activity. A GATA2 mutant not phosphorylable by 
      Akt (GATA2(S401A)) acts similarly to wild-type GATA2. In contrast, a GATA2 mutant 
      that mimics Akt phosphorylation (GATA2(S401D)) is restrained in the cytoplasm. 
      Cultured preadipocytes bearing GATA2(S401A) do not convert to adipocytes and 
      express high levels of inflammatory cytokines like monocyte chemotactic protein-1 
      (MCP-1). On the contrary, GATA2(S401D) preadipocytes differentiate to adipocytes. 
      When GATA2(S401A) preadipocytes are injected in mice fed a high-fat diet, they do 
      not differentiate adequately into adipocytes, maintaining the expression of 
      inflammatory markers like MCP-1. In contrast, injection of GATA2(S401D) 
      preadipocytes in mice fed a high-fat diet results in development of adipocytes 
      and no expression of inflammatory markers. CONCLUSIONS: GATA2 could be a new 
      target in the prevention and treatment of obesity-related inflammation and its 
      complications.
FAU - Menghini, Rossella
AU  - Menghini R
AD  - Department of Internal Medicine, University of Rome Tor Vergata, Policlinico Tor 
      Vergata-PTV University Hospital, Rome, Italy.
FAU - Marchetti, Valentina
AU  - Marchetti V
FAU - Cardellini, Marina
AU  - Cardellini M
FAU - Hribal, Marta L
AU  - Hribal ML
FAU - Mauriello, Alessandro
AU  - Mauriello A
FAU - Lauro, Davide
AU  - Lauro D
FAU - Sbraccia, Paolo
AU  - Sbraccia P
FAU - Lauro, Renato
AU  - Lauro R
FAU - Federici, Massimo
AU  - Federici M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (GATA2 Transcription Factor)
RN  - 0 (GATA2 protein, human)
RN  - 0 (Insulin)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Active Transport, Cell Nucleus/drug effects
MH  - Adipose Tissue/*cytology/pathology
MH  - Arteriosclerosis/etiology
MH  - Cell Differentiation
MH  - DNA-Binding Proteins/*metabolism
MH  - GATA2 Transcription Factor
MH  - Humans
MH  - Inflammation/*etiology
MH  - Insulin/pharmacology
MH  - Obesity/complications
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphoproteins/physiology
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Signal Transduction
MH  - Transcription Factors/*metabolism
EDAT- 2005/04/20 09:00
MHDA- 2005/11/16 09:00
CRDT- 2005/04/20 09:00
PHST- 2005/04/20 09:00 [pubmed]
PHST- 2005/11/16 09:00 [medline]
PHST- 2005/04/20 09:00 [entrez]
AID - 111/15/1946 [pii]
AID - 10.1161/01.CIR.0000161814.02942.B2 [doi]
PST - ppublish
SO  - Circulation. 2005 Apr 19;111(15):1946-53. doi: 
      10.1161/01.CIR.0000161814.02942.B2.