PMID- 16949833
OWN - NLM
STAT- MEDLINE
DCOM- 20061214
LR  - 20111117
IS  - 1043-4666 (Print)
IS  - 1043-4666 (Linking)
VI  - 35
IP  - 1-2
DP  - 2006 Jul
TI  - Protein tyrosine phosphatase 1B regulates TGF beta 1-induced Smad2 activation 
      through PI3 kinase-dependent pathway.
PG  - 88-94
AB  - Insulin is known to modulate transforming growth factor-beta (TGFbeta) signaling. 
      In this report, by using the IN Cell Analyzer 1000, the fluorescence cell imaging 
      instrument, we demonstrated that protein tyrosine phosphatase 1B (PTP1B) could 
      regulate TGFbeta1-induced Smad2 activation in a PI3 kinase-dependent manner. By 
      using the CHO cells stably expressing EGFP-Smad2, we showed that TGFbeta1 
      effectively stimulated Smad2 nuclear translocation in CHO cells. When pretreated 
      with insulin, TGFbeta1-induced Smad2 nuclear entry was dramatically decreased. 
      Furthermore, both the PI3K inhibitor LY294002 and the dominant negative AKT 
      (DN-AKT) abolished the inhibitory effects of insulin, demonstrating that the 
      inhibition of Smad2 activation by insulin was PI3K/AKT dependent. Since PTP1B 
      negatively modulates insulin signaling, we further addressed the effects of PTP1B 
      on insulin-mediated inhibition of Smad2 activation. Our data showed that 
      overexpression of PTP1B effectively attenuated insulin-induced inhibition of 
      Smad2 stimulation. Moreover, the PTP1B inhibitor, 
      3-(3,5-dibromo-4-hydroxy-benzoyl)-2-ethyl-benzofuran-6-sulfonicacid-(4-(thiazol-2-ylsulfamyl)-phenyl)-amide 
      (Compound-2), recovered insulin inhibition of Smad2 activation. In conclusion, 
      our data revealed the insulin inhibitory effects on TGFbeta1-induced Smad2 
      activation and the regulation role of PTP1B in the inhibition events.
FAU - Sun, Tao
AU  - Sun T
AD  - Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai 
      Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese 
      Academy of Sciences, Shanghai 201203, China.
FAU - Ye, Fei
AU  - Ye F
FAU - Ding, Hong
AU  - Ding H
FAU - Chen, Kaixian
AU  - Chen K
FAU - Jiang, Hualiang
AU  - Jiang H
FAU - Shen, Xu
AU  - Shen X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060901
PL  - England
TA  - Cytokine
JT  - Cytokine
JID - 9005353
RN  - 0 (Insulin)
RN  - 0 (Ligands)
RN  - 0 (SMAD2 protein, human)
RN  - 0 (Smad2 Protein)
RN  - 0 (Transforming Growth Factor beta1)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 3.1.3.48 (PTPN1 protein, human)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 1)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
SB  - IM
MH  - Animals
MH  - CHO Cells
MH  - Cricetinae
MH  - Cricetulus
MH  - Humans
MH  - Insulin/physiology
MH  - Ligands
MH  - Phosphatidylinositol 3-Kinases/*physiology
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 1
MH  - Protein Tyrosine Phosphatases/*physiology
MH  - Signal Transduction/*physiology
MH  - Smad2 Protein/*metabolism
MH  - Transforming Growth Factor beta1/*physiology
EDAT- 2006/09/05 09:00
MHDA- 2006/12/15 09:00
CRDT- 2006/09/05 09:00
PHST- 2006/04/15 00:00 [received]
PHST- 2006/07/18 00:00 [revised]
PHST- 2006/07/26 00:00 [accepted]
PHST- 2006/09/05 09:00 [pubmed]
PHST- 2006/12/15 09:00 [medline]
PHST- 2006/09/05 09:00 [entrez]
AID - S1043-4666(06)00220-1 [pii]
AID - 10.1016/j.cyto.2006.07.013 [doi]
PST - ppublish
SO  - Cytokine. 2006 Jul;35(1-2):88-94. doi: 10.1016/j.cyto.2006.07.013. Epub 2006 Sep 
      1.