Differential regulation of glycogen synthase kinase-3 beta by protein kinase C isotypes.
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.
Goode
N
N
Imperial Cancer Research Fund, Lincoln's Inn Fields, London, United Kingdom.
Hughes
K
K
Woodgett
J R
JR
Parker
P J
PJ
D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002460:Cell Line; D016758:Genes, jun; D038341:Glycogen Synthase Kinases; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008954:Models, Biological; D009132:Muscles / Q000201:enzymology; D010449:Peptide Mapping; D010748:Phosphopeptides / Q000302:isolation & purification; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism
D007527:Isoenzymes; D010748:Phosphopeptides; D016755:Proto-Oncogene Proteins c-jun; D011994:Recombinant Proteins; D011494:Protein Kinases; D038341:Glycogen Synthase Kinases; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases