Title : Constitutive activity of glycogen synthase kinase-3beta: positive regulation of steady-state levels of insulin receptor substrates-1 and -2 in adrenal chromaffin cells.

Pub. Date : 2006 Sep 19

PMID : 16870161






9 Functional Relationships(s)
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1 In cultured bovine adrenal chromaffin cells, 12-h treatment with 1-20 mM LiCl, an inhibitor of glycogen synthase kinase-3 (GSK-3), increased Ser(9) phosphorylation of GSK-3beta by approximately 44%, while decreasing insulin receptor substrate-1 (IRS-1) and IRS-2 protein levels by approximately 38 and approximately 62% in a concentration-dependent manner. Lithium Chloride insulin receptor substrate 2 Bos taurus
2 Treatment with SB216763 (0.1-30 microM for 12 h), a selective inhibitor of GSK-3, lowered IRS-1 and IRS-2 levels by approximately 38 and approximately 48%, while increasing beta-catenin protein level by approximately 47%, due to the prevention of GSK-3-induced degradation of beta-catenin by SB216763. SB 216763 insulin receptor substrate 2 Bos taurus
3 Insulin (100 nM for 24 h) increased Ser(9) phosphorylation of GSK-3beta by approximately 104%, while decreasing IRS-1 and IRS-2 levels by approximately 41 and approximately 72%; the insulin-induced Ser(9) phosphorylation of GSK-3beta, as well as down-regulations of IRS-1 and IRS-2 levels were restored to the control levels of nontreated cells at 24 h after the washout of the insulin (100 nM for 12 h)-treated cells. Serine insulin receptor substrate 2 Bos taurus
4 Either clasto-lactacystin beta-lactone or lactacystin (an inhibitor of proteasome) prevented LiCl- or SB216763-induced decreases of IRS-1 and IRS-2 levels by approximately 100 and approximately 69%, respectively. clasto-lactacystin beta-lactone insulin receptor substrate 2 Bos taurus
5 Either clasto-lactacystin beta-lactone or lactacystin (an inhibitor of proteasome) prevented LiCl- or SB216763-induced decreases of IRS-1 and IRS-2 levels by approximately 100 and approximately 69%, respectively. lactacystin insulin receptor substrate 2 Bos taurus
6 Either clasto-lactacystin beta-lactone or lactacystin (an inhibitor of proteasome) prevented LiCl- or SB216763-induced decreases of IRS-1 and IRS-2 levels by approximately 100 and approximately 69%, respectively. Lithium Chloride insulin receptor substrate 2 Bos taurus
7 Either clasto-lactacystin beta-lactone or lactacystin (an inhibitor of proteasome) prevented LiCl- or SB216763-induced decreases of IRS-1 and IRS-2 levels by approximately 100 and approximately 69%, respectively. SB 216763 insulin receptor substrate 2 Bos taurus
8 LiCl or SB216763 lowered IRS-2 mRNA level, with no effect on IRS-1 mRNA level. Lithium Chloride insulin receptor substrate 2 Bos taurus
9 LiCl or SB216763 lowered IRS-2 mRNA level, with no effect on IRS-1 mRNA level. SB 216763 insulin receptor substrate 2 Bos taurus