Glycogen synthase kinase-3beta: homologous regulation of cell surface insulin receptor level via controlling insulin receptor mRNA stability in adrenal chromaffin cells.
In cultured bovine adrenal chromaffin cells, 48 h-treatment with 20 mmol/L LiCl, 1 mmol/L valproic acid, 30 micromol/L SB216763, 30 micromol/L SB415286, or 100 nmol/L insulin, a condition that inhibits constitutive active glycogen synthase kinase-3 (GSK-3), decreased cell surface (125)I-insulin binding capacity by approximately 39%, without altering the K(d) value; LiCl, SB216763 or insulin decreased insulin receptor (IR) and IR precursor levels, attenuating insulin-induced Tyr-autophosphorylation of IR. LiCl increased inhibitory Ser9-phosphorylation of GSK-3beta at 6 h, decreasing (125)I-insulin binding at 24 h. SB216763-induced (125)I-insulin binding reduction (IC(50) = 3 micromol/L) was preceded by beta-catenin level increase by SB216763 (EC(50) = 11 micromol/L), a hallmark of GSK-3 inhibition. Insulin-induced rapid (> 1 min) Ser9-phosphorylation of GSK-3beta (Nemoto et al. 2006) was followed by approximately 48% decrease of IR level. LiCl did not stimulate endocytosis, nor proteolysis of IR. LiCl destabilized IR mRNA (t(1/2) = 9.3 vs. 6.5 h), decreasing IR mRNA level by approximately 47%, without altering IR gene transcription. Decreases of (125)I-insulin binding and IR level, as well as increased Ser9-phosphorylation of GSK-3beta were restored to the control levels by washing the test compound-treated cells. Thus, GSK-3beta regulates IR level via controlling IR mRNA stability.
Yokoo
Hiroki
H
Department of Pharmacology, Miyazaki Medical College, University of Miyazaki, Miyazaki, Japan.
Nemoto
Takayuki
T
Yanagita
Toshihiko
T
Satoh
Shinya
S
Yoshikawa
Norie
N
Maruta
Toyoaki
T
Wada
Akihiko
A
D000311:Adrenal Glands / Q000166:cytology*; D000704:Analysis of Variance; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D007328:Insulin / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D020871:RNA Stability / Q000187:drug effects / Q000502:physiology*; D011869:Radioligand Assay / Q000379:methods; D011972:Receptor, Insulin / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D004791:Enzyme Inhibitors; D007328:Insulin; D051176:beta Catenin; D014443:Tyrosine; D011972:Receptor, Insulin; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3