Role of protein kinase B and the MAP kinase cascade in mediating the EGF-dependent inhibition of glycogen synthase kinase 3 in Swiss 3T3 cells.
Epidermal growth factor (EGF), insulin-like growth factor 1 (IGF1) and phorbol myristate acetate (PMA) induce the inhibition of glycogen synthase kinase 3 (GSK3) by stimulating the phosphorylation of an N-terminal serine. Here, we show that protein kinase B (PKB) plays a key role in mediating EGF-induced inhibition of GSK3alpha and that the classical MAP kinase (MAPK) cascade has two functions in this process. Firstly, it makes a transient contribution to EGF-induced inhibition of GSK3alpha. Secondly, it shortens the duration of PKB activation and GSK3alpha inhibition. In contrast, PKB alone mediates the IGF1-induced inhibition of GSK3alpha, while the MAPK cascade mediates the inhibition of GSK3alpha by PMA.
Shaw
M
M
MRC Protein Phosphorylation Unit, Department of Biochemistry, MSI/WTB Complex, Dow Street, University of Dundee, Dundee, UK.
Cohen
P
P
D016475:3T3 Cells; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D000077191:Wortmannin
D000730:Androstadienes; D002070:Butadienes; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007328:Insulin; D009570:Nitriles; D011518:Proto-Oncogene Proteins; C113580:U 0126; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D038341:Glycogen Synthase Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; D013755:Tetradecanoylphorbol Acetate; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000077191:Wortmannin