PMID- 17664271
OWN - NLM
STAT- MEDLINE
DCOM- 20071108
LR  - 20210314
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 282
IP  - 39
DP  - 2007 Sep 28
TI  - Tumor necrosis factor receptor-1 can function through a G alpha 
      q/11-beta-arrestin-1 signaling complex.
PG  - 28549-28556
LID - S0021-9258(20)58587-6 [pii]
LID - 10.1074/jbc.M705869200 [doi]
AB  - Tumor necrosis factor-alpha (TNFalpha) is a proinflammatory cytokine secreted 
      from macrophages and adipocytes. It is well known that chronic TNFalpha exposure 
      can lead to insulin resistance both in vitro and in vivo and that elevated blood 
      levels of TNFalpha are observed in obese and/or diabetic individuals. TNFalpha 
      has many acute biologic effects, mediated by a complex intracellular signaling 
      pathway. In these studies we have identified new G-protein signaling components 
      to this pathway in 3T3-L1 adipocytes. We found that beta-arrestin-1 is associated 
      with TRAF2 (TNF receptor-associated factor 2), an adaptor protein of TNF 
      receptors, and that TNFalpha acutely stimulates tyrosine phosphorylation of G 
      alpha(q/11) with an increase in G alpha(q/11) activity. Small interfering 
      RNA-mediated knockdown of beta-arrestin-1 inhibits TNFalpha-induced tyrosine 
      phosphorylation of G alpha(q/11) by interruption of Src kinase activation. 
      TNFalpha stimulates lipolysis in 3T3-L1 adipocytes, and beta-arrestin-1 knockdown 
      blocks the effects of TNFalpha to stimulate ERK activation and glycerol release. 
      TNFalpha also led to activation of JNK with increased expression of the 
      proinflammatory gene, monocyte chemoattractant protein-1 and matrix 
      metalloproteinase 3, and beta-arrestin-1 knockdown inhibited both of these 
      effects. Taken together these results reveal novel elements of TNFalpha action; 
      1) the trimeric G-protein component G alpha(q/11) and the adapter protein 
      beta-arrestin-1 can function as signaling molecules in the TNFalpha action 
      cascade; 2) beta-arrestin-1 can couple TNFalpha stimulation to ERK activation and 
      lipolysis; 3) beta-arrestin-1 and G alpha(q/11) can mediate TNFalpha-induced 
      phosphatidylinositol 3-kinase activation and inflammatory gene expression.
FAU - Kawamata, Yuji
AU  - Kawamata Y
AD  - Department of Medicine, Division of Endocrinology and Metabolism, University of 
      California, San Diego, La Jolla, California 92093-0673.
FAU - Imamura, Takeshi
AU  - Imamura T
AD  - Department of Medicine, Division of Endocrinology and Metabolism, University of 
      California, San Diego, La Jolla, California 92093-0673.
FAU - Babendure, Jennie L
AU  - Babendure JL
AD  - Department of Medicine, Division of Endocrinology and Metabolism, University of 
      California, San Diego, La Jolla, California 92093-0673.
FAU - Lu, Juu-Chin
AU  - Lu JC
AD  - Department of Medicine, Division of Endocrinology and Metabolism, University of 
      California, San Diego, La Jolla, California 92093-0673.
FAU - Yoshizaki, Takeshi
AU  - Yoshizaki T
AD  - Department of Medicine, Division of Endocrinology and Metabolism, University of 
      California, San Diego, La Jolla, California 92093-0673.
FAU - Olefsky, Jerrold M
AU  - Olefsky JM
AD  - Department of Medicine, Division of Endocrinology and Metabolism, University of 
      California, San Diego, La Jolla, California 92093-0673. Electronic address: 
      jolefsky@ucsd.edu.
LA  - eng
GR  - DK33651/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070730
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (ARRB1 protein, human)
RN  - 0 (Arrb1 protein, mouse)
RN  - 0 (Arrestins)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Tnfrsf1a protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (beta-Arrestin 1)
RN  - 0 (beta-Arrestins)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 3.6.5.1 (GTP-Binding Protein alpha Subunits, Gq-G11)
RN  - PDC6A3C0OX (Glycerol)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/*metabolism
MH  - Animals
MH  - Arrestins/*metabolism
MH  - Diabetes Complications/metabolism
MH  - Enzyme Activation/drug effects
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - GTP-Binding Protein alpha Subunits, Gq-G11/*metabolism
MH  - Glycerol/metabolism
MH  - Humans
MH  - Inflammation Mediators/metabolism
MH  - Insulin Resistance
MH  - Lipolysis/drug effects
MH  - MAP Kinase Signaling System/*drug effects
MH  - Mice
MH  - Multiprotein Complexes/*metabolism
MH  - Obesity/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation/drug effects
MH  - Receptors, Tumor Necrosis Factor, Type I/*metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism/*pharmacology
MH  - beta-Arrestin 1
MH  - beta-Arrestins
EDAT- 2007/08/01 09:00
MHDA- 2007/11/09 09:00
CRDT- 2007/08/01 09:00
PHST- 2007/08/01 09:00 [pubmed]
PHST- 2007/11/09 09:00 [medline]
PHST- 2007/08/01 09:00 [entrez]
AID - S0021-9258(20)58587-6 [pii]
AID - 10.1074/jbc.M705869200 [doi]
PST - ppublish
SO  - J Biol Chem. 2007 Sep 28;282(39):28549-28556. doi: 10.1074/jbc.M705869200. Epub 
      2007 Jul 30.