Inactivation of glycogen synthase kinase-3β by phosphorylation: new kinase connections in insulin and growth-factor signalling
- 15 November 1993
- journal article
- Published by Portland Press Ltd. in Biochemical Journal
- Vol. 296 (1) , 15-19
- https://doi.org/10.1042/bj2960015
Abstract
The beta-isoform of glycogen synthase kinase-3 (GSK3 beta) 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 (p70S6K), and re-activated with protein phosphatase 2A. MAPKAP kinase-1 and p70S6K phosphorylated the same tryptic peptide on GSK3 beta, 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 GSK3 beta 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 GSK3 beta by insulin and that GSK3 may represent a point of convergence of two major growth-factor-stimulated protein kinase cascades.Keywords
This publication has 32 references indexed in Scilit:
- An analysis of the substrate specificity of insulin-stimulated protein kinase-1, a mammalian homologue of S6 kinase-IIBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1993
- Glycogen synthase kinase-3: functions in oncogenesis and developmentBiochimica et Biophysica Acta (BBA) - Reviews on Cancer, 1992
- wingless signaling acts through zeste-white 3, the drosophila homolog of glycogen synthase kinase-3, to regulate engrailed and establish cell fateCell, 1992
- Identification of MAPKAP kinase 2 as a major enzyme responsible for the phosphorylation of the small mammalian heat shock proteinsFEBS Letters, 1992
- Purification and characterisation of the insulin‐stimulated protein kinase from rabbit skeletal muscle; close similarity to S6 kinase IIEuropean Journal of Biochemistry, 1991
- The molecular mechanism by which insulin stimulates glycogen synthesis in mammalian skeletal muscleNature, 1990
- Glycogen Synthase from Rabbit Skeletal Muscle; Effect of Insulin on the State of phosphorylation of the Seven Phosphoserine Residues in vivoEuropean Journal of Biochemistry, 1983
- Reconstitution of a Mg‐ATP‐dependent protein phosphatase and its activation through a phosphorylation mechanismFEBS Letters, 1982
- Multisite phosphorylation of glycogen synthase from rabbit skeletal muscleFEBS Letters, 1982
- A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye BindingAnalytical Biochemistry, 1976