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• W2050721506 abstract "In cultured bovine adrenal chromaffin cells, ∼24 h-treatment with insulin-like growth factor-I (IGF-I) decreased cell surface 125I-IGF-I binding capacity and IGF-I receptor protein level by ∼64% (EC50 = 5.0 nM; t1/2 = ∼7 h). IGF-I-induced IGF-I receptor decrease was abolished by LY294002 (phosphoinositide 3-kinase inhibitor) and partially attenuated by rapamycin (an inhibitor of mammalian target of rapamycin [mTOR]). SB216763 (an inhibitor of glycogen synthase kinase-3 [GSK-3]) down-regulated IGF-I receptor, which was further decreased by IGF-I. IGF-I increased inhibitory Ser9-phosphorylation of GSK-3β and stimulatory Ser2448-phosphorylation of mTOR. l-leucine increased phosphorylation of mTOR (but not GSK-3β), and down-regulated IGF-I receptor, both events being abolished by rapamycin. IGF-I-induced IGF-I receptor decrease was not prevented by proteolysis inhibitors. Pulse-label with [35S]methionine/cysteine followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that SB216763 or l-leucine retarded synthesis of IGF-I receptor and its precursor molecule. SB216763 (but not l-leucine) destabilized IGF-I receptor mRNA and decreased its level, without changing IGF-I receptor gene transcription. In SB216763-treated cells, IGF-I-induced Tyr-autophosphorylation of IGF-I receptor was decreased by 36%, compared to nontreated cells. IGF-I attenuated constitutive Ser396-phosphorylation of tau by 30% in nontreated cells, but not in SB216763-treated cells. IGF-I-induced down-regulations of 125I-IGF-I binding and IGF-I receptor, as well as IGF-I-induced phosphorylations of GSK-3β and mTOR were restored to the control levels of nontreated cells after washout of IGF-I (10 nM for 12 h)-treated cells. Thus, IGF-I down-regulated functional IGF-I receptor via GSK-3β inhibition and mTOR activation; constitutive activity of GSK-3β maintained IGF-I receptor level in nonstimulated cells." @default.
• W2050721506 created "2016-06-24" @default.
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• W2050721506 date "2010-06-01" @default.
• W2050721506 modified "2023-10-17" @default.
• W2050721506 title "Homologous posttranscriptional regulation of insulin-like growth factor-I receptor level via glycogen synthase kinase-3β and mammalian target of rapamycin in adrenal chromaffin cells: Effect on tau phosphorylation" @default.
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• W2050721506 doi "https://doi.org/10.1016/j.neuropharm.2010.01.018" @default.
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