Phosphorylation of IRS1 at serine 307 and serine 312 in response to insulin in human adipocytes.
Feedback control in insulin signaling involves serine phosphorylation of insulin receptor substrate-1 (IRS1). By analyzing the insulin-induced phosphorylation of IRS1 at serine 307, serine 312, and tyrosine in the same primary human adipocytes, we now report that negative feedback phosphorylation of serine 312 (corresponding to murine serine 307) required relatively high concentrations of insulin (EC(50)=3 nM) for a long time (t(1/2) ca. 30 min) and reduced the steady-state tyrosine phosphorylation, without affecting the cellular concentration, of IRS1. In contrast, positive feedback phosphorylation of serine 307 was a rapid (t(1/2) ca. 2 min) event at physiological concentrations of insulin (EC(50)=0.2 nM).
Danielsson
Anna
A
Department of Cell Biology and Diabetes Research Centre, Linköping University, SE58185 Linköping, Sweden.
Nystrom
Fredrik H
FH
Strålfors
Peter
P
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D000368:Aged; D001665:Binding Sites; D002478:Cells, Cultured; D005246:Feedback; D005260:Female; D006801:Humans; D007328:Insulin / Q000008:administration & dosage*; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance / Q000502:physiology*; D008875:Middle Aged; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D012694:Serine / Q000737:chemistry / Q000378:metabolism*
C526292:IRS1 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; D012694:Serine