Human, but not rat, IRS1 targets to the plasma membrane in both human and rat adipocytes.
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.
Stenkula
Karin G
KG
Department of Cell Biology, Linköping University, SE58185 Linköping, Sweden.
Thorn
Hans
H
Franck
Niclas
N
Hallin
Elisabeth
E
Sauma
Lilian
L
Nystrom
Fredrik H
FH
Strålfors
Peter
P
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D055504:Insulin Receptor Substrate Proteins; D008297:Male; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D010957:Plasmids / Q000235:genetics; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D011993:Recombinant Fusion Proteins