Differential regulation of glycogen synthase kinase-3 beta by protein kinase C isotypes

• Published in: The Journal of biological chemistry Vol. 267; no. 24; pp. 16878 - 16882
• Main Authors: GOODE, N, HUGHES, K, WOODGETT, J. R, PARKER, P. J
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 25.08.1992
• Subjects: activation; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Calcium-Calmodulin-Dependent Protein Kinases; Cell Line; cells; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Genes, jun; glycogen synthase kinase-3 beta; Glycogen Synthase Kinases; HeLa Cells; Homeostasis; Humans; Isoenzymes - metabolism; Models, Biological; Muscles - enzymology; Peptide Mapping; Phosphopeptides - isolation & purification; Phosphorylation; protein kinase C; Protein Kinase C - metabolism; Protein Kinases - metabolism; Proto-Oncogene Proteins c-jun - genetics; Proto-Oncogene Proteins c-jun - metabolism; Recombinant Proteins - metabolism; regulation; Transferases; Signal transduction; Phosphorylation; Protein kinase C; Enzyme; C-Onc gene; Transcription factor; Inactivation; Glycogen synthase kinase
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(18)41866-2

In cells, stimulation of protein kinase C (PKC) results in the dephosphorylation of specific residues proximal to the DNA binding domain of c-Jun, a major component of the AP-1 transcription factor. Since phosphorylation of this region of c-Jun inhibits interaction with DNA, this pathway may contribute to PKC activation of AP-1. To determine the mechanism(s) underlying this pathway, possible interactions between PKC and proteins implicated in c-Jun regulation are being investigated. Here it is shown that glycogen synthase kinase-3 beta (GSK-3 beta), a serine/threonine kinase that specifically targets the inhibitory c-Jun phosphorylation sites, is phosphorylated in vitro by particular forms of PKC (alpha, beta 1, gamma greater than beta 2; not epsilon). By contrast, the related GSK-3 alpha is not a substrate for any of these PKC isotypes. Phosphorylation of GSK-3 beta by PKC results in its specific inactivation. These results are consistent with a model in which activation of PKC stimulates c-Jun DNA binding by inhibiting its phosphorylation by GSK-3 beta.