PMID- 11724774
OWN - NLM
STAT- MEDLINE
DCOM- 20020401
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 277
IP  - 9
DP  - 2002 Mar 1
TI  - Insulin receptor substrate-3 functions as transcriptional activator in the 
      nucleus.
PG  - 6846-51
AB  - The family of insulin receptor substrates (IRSs) has been reported to play 
      important roles for signal transduction of various hormones. Four members of the 
      IRS family have been described. Each IRS is believed to have different functions; 
      however, the distinct physiological roles of each IRS are unclear. This study was 
      undertaken to determine the intracellular localization of IRS-3. IRS-3 was 
      expressed in COS-7 cells as fusion with a green fluorescent protein (GFP), and 
      subcellular localization of the chimera protein was analyzed by fluorescent 
      microscopy. Surprisingly, GFP-IRS-3 was localized not only adjacent to the plasma 
      membrane but also in the nucleus. We confirmed by immunostaining with anti-IRS-3 
      antibody that non-fused IRS-3 protein is also localized in the nucleus of COS-7 
      cells that were transfected with IRS-3 cDNA. In addition, we detected endogenous 
      IRS-3 in the nucleus of isolated rat adipocytes. We then studied subcellular 
      localization of deletion mutants and fragments of IRS-3 fused with GFP. We found 
      that the region corresponding to amino acid residues 192-223 in the 
      phosphotyrosine binding domain played an important role in nuclear localization. 
      This region includes sequences that are unique to IRS-3. We then investigated 
      intracellular localization of other IRSs fused with GFP. GFP-IRS-1, GFP-IRS-2, 
      and GFP-IRS-4 were mainly localized in the cytosol or plasma membranes. Chimeric 
      protein, Gal4 DNA binding domain fused with IRS-3 C-terminal region, increased 
      transcription of the reporter gene containing Gal4 binding site in human 
      embryonic kidney 293 cells. These results suggest that intracellular localization 
      of IRS-3 is determined by a different mechanism from other IRS proteins, and that 
      IRS-3 possesses a transcription-regulating activity.
FAU - Kabuta, Tomohiro
AU  - Kabuta T
AD  - Department of Animal Sciences, Graduate School of Agriculture and Life Sciences, 
      The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
FAU - Hakuno, Fumihiko
AU  - Hakuno F
FAU - Asano, Tomoichiro
AU  - Asano T
FAU - Takahashi, Shin-Ichiro
AU  - Takahashi S
LA  - eng
PT  - Journal Article
DEP - 20011127
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA, Complementary)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Fungal Proteins)
RN  - 0 (GAL4 protein, S cerevisiae)
RN  - 0 (IRS3P protein, human)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Irs3 protein, rat)
RN  - 0 (Luminescent Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 0 (Transcription Factors)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 3.2.1.23 (beta-Galactosidase)
SB  - IM
MH  - Adipocytes/metabolism
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites
MH  - COS Cells
MH  - Cell Membrane/metabolism
MH  - Cell Nucleus/*metabolism
MH  - Cytosol/metabolism
MH  - DNA, Complementary/metabolism
MH  - DNA-Binding Proteins
MH  - Fungal Proteins/metabolism
MH  - Green Fluorescent Proteins
MH  - Humans
MH  - Immunoblotting
MH  - Insulin Receptor Substrate Proteins
MH  - Luciferases/metabolism
MH  - Luminescent Proteins/metabolism
MH  - Microscopy, Fluorescence
MH  - Molecular Sequence Data
MH  - Phosphoproteins/*metabolism/*physiology
MH  - Plasmids/metabolism
MH  - Precipitin Tests
MH  - Protein Structure, Tertiary
MH  - Rats
MH  - Rats, Wistar
MH  - Recombinant Fusion Proteins/metabolism
MH  - *Saccharomyces cerevisiae Proteins
MH  - Sequence Homology, Amino Acid
MH  - Subcellular Fractions/metabolism
MH  - Transcription Factors/metabolism
MH  - *Transcription, Genetic
MH  - Transfection
MH  - beta-Galactosidase/metabolism
EDAT- 2001/11/29 10:00
MHDA- 2002/04/02 10:01
CRDT- 2001/11/29 10:00
PHST- 2001/11/29 10:00 [pubmed]
PHST- 2002/04/02 10:01 [medline]
PHST- 2001/11/29 10:00 [entrez]
AID - S0021-9258(19)82229-9 [pii]
AID - 10.1074/jbc.M107058200 [doi]
PST - ppublish
SO  - J Biol Chem. 2002 Mar 1;277(9):6846-51. doi: 10.1074/jbc.M107058200. Epub 2001 
      Nov 27.