Inactivation of glycogen synthase kinase-3β by phosphorylation: New kinase connections in insulin and growth-factor signalling

TY - JOUR

T1 - Inactivation of glycogen synthase kinase-3β by phosphorylation

T2 - New kinase connections in insulin and growth-factor signalling

AU - Sutherland, C.

AU - Leighton, I. A.

AU - Cohen, P.

PY - 1993/11/15

Y1 - 1993/11/15

N2 - The β-isoform of glycogen synthase kinase-3 (GSK3β) isolated from rabbit skeletal muscle was inactivated 90-95% following incubation with MgATP and either MAP kinase-activated protein kinase-1 (MAPKAP kinase-1, also termed RSK-2) or p70 S6 kinase (p70(S6K)), and re-activated with protein phosphatase 2A. MAPKAP kinase-1 and p70(S6K) phosphorylated the same tryptic peptide on GSK3β and the site of phosphorylation was identified as the serine located nine residues from the N-terminus of the protein. The inhibitory effect of Ser-9 phosphorylation on GSK3β activity was observed with three substrates, (inhibitor-2, c-jun and a synthetic peptide), and also with glycogen synthase provided that 0.15 M KCl was added to the assays. The results suggest that Ser-9 phosphorylation underlies the reported inhibition of GSK3β by insulin and that GSK3 may represent a point of convergence of two major growth-factor-stimulated protein kinase cascades.

AB - The β-isoform of glycogen synthase kinase-3 (GSK3β) isolated from rabbit skeletal muscle was inactivated 90-95% following incubation with MgATP and either MAP kinase-activated protein kinase-1 (MAPKAP kinase-1, also termed RSK-2) or p70 S6 kinase (p70(S6K)), and re-activated with protein phosphatase 2A. MAPKAP kinase-1 and p70(S6K) phosphorylated the same tryptic peptide on GSK3β and the site of phosphorylation was identified as the serine located nine residues from the N-terminus of the protein. The inhibitory effect of Ser-9 phosphorylation on GSK3β activity was observed with three substrates, (inhibitor-2, c-jun and a synthetic peptide), and also with glycogen synthase provided that 0.15 M KCl was added to the assays. The results suggest that Ser-9 phosphorylation underlies the reported inhibition of GSK3β by insulin and that GSK3 may represent a point of convergence of two major growth-factor-stimulated protein kinase cascades.

UR - https://www.scopus.com/pages/publications/0027515127

U2 - 10.1042/bj2960015

DO - 10.1042/bj2960015

M3 - Article

C2 - 8250835

AN - SCOPUS:0027515127

SN - 0264-6021

VL - 296

SP - 15

EP - 19

JO - Biochemical Journal

JF - Biochemical Journal

IS - 1

ER -