Epidermal growth factor inhibits glycogen synthase kinase-3 (GSK-3) and β-catenin transcription in cultured ARPE-19 cells

2007 ◽  
Vol 245 (10) ◽  
pp. 1543-1548 ◽  
Author(s):  
Walter Krugluger ◽  
Stefan Seidel ◽  
Kerstin Steindl ◽  
Susanne Binder
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Epidermal Growth

scholarly journals The mechanism by which epidermal growth factor inhibits glycogen synthase kinase 3 in A431 cells

1994 ◽  
Vol 303 (1) ◽  
pp. 27-31 ◽  
Author(s):  
Y Saito ◽  
J R Vandenheede ◽  
P Cohen
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
A431 Cells ◽  
S6 Kinase ◽  
P70 S6 Kinase ◽  
Epidermal Growth

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.

scholarly journals Functional Effects of PTPN11 (SHP2) Mutations Causing LEOPARD Syndrome on Epidermal Growth Factor-Induced Phosphoinositide 3-Kinase/AKT/Glycogen Synthase Kinase 3β Signaling

2010 ◽  
Vol 30 (10) ◽  
pp. 2498-2507 ◽  
Author(s):  
Thomas Edouard ◽  
Jean-Philippe Combier ◽  
Audrey Nédélec ◽  
Sophie Bel-Vialar ◽  
Mélanie Métrich ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Hek293 Cells ◽  
Glycogen Synthase Kinase 3Β ◽  
Leopard Syndrome ◽  
Epidermal Growth ◽  
Gsk 3Β ◽  
Phosphoinositide 3 Kinase

ABSTRACT LEOPARD syndrome (LS), a disorder with multiple developmental abnormalities, is mainly due to mutations that impair the activity of the tyrosine phosphatase SHP2 (PTPN11). How these alterations cause the disease remains unknown. We report here that fibroblasts isolated from LS patients displayed stronger epidermal growth factor (EGF)-induced phosphorylation of both AKT and glycogen synthase kinase 3β (GSK-3β) than fibroblasts from control patients. Similar results were obtained in HEK293 cells expressing LS mutants of SHP2. We found that the GAB1/phosphoinositide 3-kinase (PI3K) complex was more abundant in fibroblasts from LS than control subjects and that both AKT and GSK-3β hyperphosphorylation were prevented by reducing GAB1 expression or by overexpressing a GAB1 mutant unable to bind to PI3K. Consistently, purified recombinant LS mutants failed to dephosphorylate GAB1 PI3K-binding sites. These mutants induced PI3K-dependent increase in cell size in a model of chicken embryo cardiac explants and in transcriptional activity of the atrial natriuretic factor (ANF) gene in neonate rat cardiomyocytes. In conclusion, SHP2 mutations causing LS facilitate EGF-induced PI3K/AKT/GSK-3β stimulation through impaired GAB1 dephosphorylation, resulting in deregulation of a novel signaling pathway that could be involved in LS pathology.

scholarly journals The Fibroblast Growth Factor 14·Voltage-gated Sodium Channel Complex Is a New Target of Glycogen Synthase Kinase 3 (GSK3)

2013 ◽  
Vol 288 (27) ◽  
pp. 19370-19385 ◽  
Author(s):  
Alexander S. Shavkunov ◽  
Norelle C. Wildburger ◽  
Miroslav N. Nenov ◽  
Thomas F. James ◽  
Tetyana P. Buzhdygan ◽  
...  
Keyword(s):  
Growth Factor ◽  
Sodium Channel ◽  
Fibroblast Growth Factor ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Fibroblast Growth ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated
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