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Human, but not rat, IRS1 targets to the plasma membrane in both human and rat adipocytes

Stenkula, Karin G LU ; Thorn, Hans ; Franck, Niclas ; Hallin, Elisabeth ; Sauma, Lilian ; Nystrom, Fredrik H and Strålfors, Peter (2007) In Biochemical and Biophysical Research Communications 363(3). p.5-840
Abstract

Adipocytes are primary targets for insulin control of metabolism. The activated insulin receptor phosphorylates insulin receptor substrate-1 (IRS1), which acts as a docking protein for downstream signal mediators. In the absence of insulin stimulation, IRS1 in rat adipocytes is intracellular but in human adipocytes IRS1 is constitutively targeted to the plasma membrane. Stimulation of adipocytes with insulin increased the amount of IRS1 at the plasma membrane 2-fold in human adipocytes, but >10-fold in rat adipocytes, with the same final amount of IRS1 at the plasma membrane in cells from both species. Cross-transfection of rat adipocytes with human IRS1, or human adipocytes with rat IRS1, demonstrated that the species difference was... (More)

Adipocytes are primary targets for insulin control of metabolism. The activated insulin receptor phosphorylates insulin receptor substrate-1 (IRS1), which acts as a docking protein for downstream signal mediators. In the absence of insulin stimulation, IRS1 in rat adipocytes is intracellular but in human adipocytes IRS1 is constitutively targeted to the plasma membrane. Stimulation of adipocytes with insulin increased the amount of IRS1 at the plasma membrane 2-fold in human adipocytes, but >10-fold in rat adipocytes, with the same final amount of IRS1 at the plasma membrane in cells from both species. Cross-transfection of rat adipocytes with human IRS1, or human adipocytes with rat IRS1, demonstrated that the species difference was due to the IRS1 protein and not the cellular milieus or posttranslational modifications. Chimeric IRS1, consisting of the conserved N-terminus of rat IRS1 with the variable C-terminal of human IRS1, did not target the plasma membrane, indicating that subtle sequence differences direct human IRS1 to the plasma membrane.

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author
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publishing date
type
Contribution to journal
publication status
published
keywords
Adaptor Proteins, Signal Transducing/genetics, Adipocytes/cytology, Animals, Cell Membrane/metabolism, Cells, Cultured, Insulin Receptor Substrate Proteins, Male, Microscopy, Confocal, Microscopy, Electron, Transmission, Plasmids/genetics, Protein Transport, Rats, Rats, Sprague-Dawley, Recombinant Fusion Proteins/genetics, Transfection
in
Biochemical and Biophysical Research Communications
volume
363
issue
3
pages
5 - 840
publisher
Elsevier
external identifiers
  • scopus:34848907968
  • pmid:17905199
ISSN
0006-291X
DOI
10.1016/j.bbrc.2007.09.065
language
English
LU publication?
no
id
7eafce69-210c-4813-98ee-f72ad7277269
date added to LUP
2021-05-20 15:10:23
date last changed
2024-01-05 11:15:09
@article{7eafce69-210c-4813-98ee-f72ad7277269,
  abstract     = {{<p>Adipocytes are primary targets for insulin control of metabolism. The activated insulin receptor phosphorylates insulin receptor substrate-1 (IRS1), which acts as a docking protein for downstream signal mediators. In the absence of insulin stimulation, IRS1 in rat adipocytes is intracellular but in human adipocytes IRS1 is constitutively targeted to the plasma membrane. Stimulation of adipocytes with insulin increased the amount of IRS1 at the plasma membrane 2-fold in human adipocytes, but &gt;10-fold in rat adipocytes, with the same final amount of IRS1 at the plasma membrane in cells from both species. Cross-transfection of rat adipocytes with human IRS1, or human adipocytes with rat IRS1, demonstrated that the species difference was due to the IRS1 protein and not the cellular milieus or posttranslational modifications. Chimeric IRS1, consisting of the conserved N-terminus of rat IRS1 with the variable C-terminal of human IRS1, did not target the plasma membrane, indicating that subtle sequence differences direct human IRS1 to the plasma membrane.</p>}},
  author       = {{Stenkula, Karin G and Thorn, Hans and Franck, Niclas and Hallin, Elisabeth and Sauma, Lilian and Nystrom, Fredrik H and Strålfors, Peter}},
  issn         = {{0006-291X}},
  keywords     = {{Adaptor Proteins, Signal Transducing/genetics; Adipocytes/cytology; Animals; Cell Membrane/metabolism; Cells, Cultured; Insulin Receptor Substrate Proteins; Male; Microscopy, Confocal; Microscopy, Electron, Transmission; Plasmids/genetics; Protein Transport; Rats; Rats, Sprague-Dawley; Recombinant Fusion Proteins/genetics; Transfection}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{5--840}},
  publisher    = {{Elsevier}},
  series       = {{Biochemical and Biophysical Research Communications}},
  title        = {{Human, but not rat, IRS1 targets to the plasma membrane in both human and rat adipocytes}},
  url          = {{http://dx.doi.org/10.1016/j.bbrc.2007.09.065}},
  doi          = {{10.1016/j.bbrc.2007.09.065}},
  volume       = {{363}},
  year         = {{2007}},
}