The mechanism by which epidermal growth factor inhibits glycogen synthase kinase 3 in A431 cells.
Glycogen synthase kinase 3 (GSK3) was inhibited by 50% within 5 min when A431 cells were stimulated with epidermal growth factor (EGF). The inhibition was unaffected by rapamycin at concentrations which blocked the activation of p70 S6 kinase, and reversed by incubation with protein phosphatase-1. EGF stimulation of A431 cells inhibited GSK3 alpha and GSK3 beta to a similar extent, and inhibition was accompanied by phosphorylation of the tryptic peptides containing the serine residues phosphorylated in vitro by p70 S6 kinase or MAP kinase-activated protein (MAPKAP) kinase-1 beta (also termed Rsk-2). These results demonstrate that EGF inhibits GSK3 by inducing phosphorylation of a serine residue and that GSK3 is not phosphorylated in vivo by either p70 S6 kinase or protein kinase C.
Saito
Y
Y
Department of Biochemistry, University of Dundee, Scotland, U.K.
Vandenheede
J R
JR
Cohen
P
P
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007700:Kinetics; D019319:Okadaic Acid; D010710:Phosphates / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D010769:Phosphothreonine / Q000378:metabolism; D011090:Polyenes / Q000494:pharmacology; D054645:Protein Phosphatase 1; D011865:Radioisotope Dilution Technique; D020123:Sirolimus; D014407:Tumor Cells, Cultured
D004988:Ethers, Cyclic; D007166:Immunosuppressive Agents; D010710:Phosphates; D010761:Phosphorus Radioisotopes; D011090:Polyenes; D010769:Phosphothreonine; D010768:Phosphoserine; D019319:Okadaic Acid; D004815:Epidermal Growth Factor; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D020123:Sirolimus