PMID- 11136729
OWN - NLM
STAT- MEDLINE
DCOM- 20010510
LR  - 20211203
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 276
IP  - 13
DP  - 2001 Mar 30
TI  - Protein-tyrosine phosphatase-1B negatively regulates insulin signaling in l6 
      myocytes and Fao hepatoma cells.
PG  - 10207-11
AB  - Insulin signaling is regulated by tyrosine phosphorylation of the signaling 
      molecules, such as the insulin receptor and insulin receptor substrates (IRSs). 
      Therefore, the balance between protein-tyrosine kinases and protein-tyrosine 
      phosphatase activities is thought to be important in the modulation of insulin 
      signaling in insulin-resistant states. We thus employed the adenovirus-mediated 
      gene transfer technique, and we analyzed the effect of overexpression of a 
      wild-type protein-tyrosine phosphatase-1B (PTP1B) on insulin signaling in both L6 
      myocytes and Fao cells. In both cells, PTP1B overexpression blocked 
      insulin-stimulated tyrosine phosphorylation of the insulin receptor and IRS-1 by 
      more than 70% and resulted in a significant inhibition of the association between 
      IRS-1 and the p85 subunit of phosphatidylinositol 3-kinase and Akt 
      phosphorylation as well as mitogen-activated protein kinase phosphorylation. 
      Moreover, insulin-stimulated glycogen synthesis was also inhibited by PTP1B 
      overexpression in both cells. These effects were specific for insulin signaling, 
      because platelet-derived growth factor (PDGF)-stimulated PDGF receptor tyrosine 
      phosphorylation and Akt phosphorylation were not inhibited by PTP1B 
      overexpression. The present findings demonstrate that PTP1B negatively regulates 
      insulin signaling in L6 and Fao cells, suggesting that PTP1B plays an important 
      role in insulin resistance in muscle and liver.
FAU - Egawa, K
AU  - Egawa K
AD  - Third Department of Medicine, Shiga University of Medical Science, Otsu, Shiga 
      520-2192, Japan.
FAU - Maegawa, H
AU  - Maegawa H
FAU - Shimizu, S
AU  - Shimizu S
FAU - Morino, K
AU  - Morino K
FAU - Nishio, Y
AU  - Nishio Y
FAU - Bryer-Ash, M
AU  - Bryer-Ash M
FAU - Cheung, A T
AU  - Cheung AT
FAU - Kolls, J K
AU  - Kolls JK
FAU - Kikkawa, R
AU  - Kikkawa R
FAU - Kashiwagi, A
AU  - Kashiwagi A
LA  - eng
GR  - RR-00211/RR/NCRR 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 - 20010102
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (IRS1 protein, human)
RN  - 0 (Insulin)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 9005-79-2 (Glycogen)
RN  - EC 2.4.1.11 (Glycogen Synthase)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
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)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Blotting, Western
MH  - Carcinoma, Hepatocellular/metabolism
MH  - Cell Line
MH  - Gene Transfer Techniques
MH  - Glycogen/metabolism
MH  - Glycogen Synthase/metabolism
MH  - Humans
MH  - Insulin/*metabolism
MH  - Insulin Receptor Substrate Proteins
MH  - Insulin Resistance
MH  - Liver/metabolism
MH  - Liver Neoplasms/metabolism
MH  - Muscles/metabolism
MH  - Myocardium/*cytology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphoproteins/metabolism
MH  - Phosphorylation
MH  - Platelet-Derived Growth Factor/metabolism
MH  - *Protein Serine-Threonine Kinases
MH  - Protein Tyrosine Phosphatases/*metabolism
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - *Signal Transduction
MH  - Tumor Cells, Cultured
EDAT- 2001/01/14 19:15
MHDA- 2001/05/22 10:01
CRDT- 2001/01/14 19:15
PHST- 2001/01/14 19:15 [pubmed]
PHST- 2001/05/22 10:01 [medline]
PHST- 2001/01/14 19:15 [entrez]
AID - S0021-9258(19)34292-9 [pii]
AID - 10.1074/jbc.M009489200 [doi]
PST - ppublish
SO  - J Biol Chem. 2001 Mar 30;276(13):10207-11. doi: 10.1074/jbc.M009489200. Epub 2001 
      Jan 2.