scholarly journals Lithium Can Relieve Translational Repression of TOP mRNAs Elicited by Various Blocks along the Cell Cycle in a Glycogen Synthase Kinase-3- and S6-Kinase-independent Manner

2004 ◽  
Vol 280 (7) ◽  
pp. 5336-5342 ◽  
Author(s):  
Miri Stolovich ◽  
Tal Lerer ◽  
Yoav Bolkier ◽  
Hannah Cohen ◽  
Oded Meyuhas
Keyword(s):  
Cell Cycle ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Translational Repression ◽  
Glycogen Synthase Kinase 3 ◽  
Independent Manner ◽  
S6 Kinase

scholarly journals Glycogen Synthase Kinase 3 Phosphorylates Hypoxia-Inducible Factor 1α and Mediates Its Destabilization in a VHL-Independent Manner

2007 ◽  
Vol 27 (9) ◽  
pp. 3253-3265 ◽  
Author(s):  
Daniela Flügel ◽  
Agnes Görlach ◽  
Carine Michiels ◽  
Thomas Kietzmann
Keyword(s):  
Protein Kinase ◽  
Metabolic Diseases ◽  
Glycogen Synthase ◽  
Protein Kinase B ◽  
Hypoxia Inducible Factor ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Independent Manner ◽  
Von Hippel Lindau ◽  
Gsk 3Β

ABSTRACT Hypoxia-inducible transcription factor 1α (HIF-1α) is a key player in the response to hypoxia. Additionally, HIF-1α responds to growth factors and hormones which can act via protein kinase B (Akt). However, HIF-1α is not a direct substrate for this kinase. Therefore, we investigated whether the protein kinase B target glycogen synthase kinase 3 (GSK-3) may have an impact on HIF-1α. We found that the inhibition or depletion of GSK-3 induced HIF-1α whereas the overexpression of GSK-3β reduced HIF-1α. These effects were mediated via three amino acid residues in the oxygen-dependent degradation domain of HIF-1α. In addition, mutation analyses and experiments with von Hippel-Lindau (VHL)-defective cells indicated that GSK-3 mediates HIF-1α degradation in a VHL-independent manner. In line with these observations, the inhibition of the proteasome reversed the GSK-3 effects, indicating that GSK-3 may target HIF-1α to the proteasome by phosphorylation. Thus, the direct regulation of HIF-1α stability by GSK-3 may influence physiological processes or pathophysiological situations such as metabolic diseases or tumors.

scholarly journals Wortmannin inhibits the effects of insulin and serum on the activities of glycogen synthase kinase-3 and mitogen-activated protein kinase

1994 ◽  
Vol 303 (1) ◽  
pp. 15-20 ◽  
Author(s):  
G I Welsh ◽  
E J Foulstone ◽  
S W Young ◽  
J M Tavaré ◽  
C G Proud
Keyword(s):  
Map Kinase ◽  
Phorbol Ester ◽  
Glycogen Synthase ◽  
Chinese Hamster Ovary Cells ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Parental Cell Line ◽  
S6 Kinase ◽  
Mitogen Activated Protein ◽  
Kinase Pathway

We have previously shown that insulin causes inactivation of glycogen synthase kinase-3 (GSK-3) in Chinese hamster ovary cells over-expressing the human insulin receptor (CHO.T cells). We now show that serum and phorbol ester also cause rapid inactivation of GSK-3, both in CHO.T cells and in the nontransfected parental cell line, CHO.K1 cells. Rapamycin was without effect on the inactivation of GSK-3 by insulin, serum or phorbol ester, indicating that the p70 S6 kinase pathway is not involved. In contrast, wortmannin, a potent inhibitor of phosphatidylinositol 3-kinase, blocked the effects of both insulin and serum on GSK-3 activity, and also substantially reduced the activation of both p90 S6 kinase (by insulin) and mitogen-activated protein (MAP) kinase (by insulin and serum). These findings imply (i) that GSK-3 activity is regulated by a cascade involving MAP kinase and p90 S6 kinase and (ii) that wortmannin affects an early step in the MAP kinase pathway. One can infer from this that GSK-3 may be an important regulatory enzyme for the control of several biosynthetic pathways, key enzymes in which are regulated by GSK-3-mediated phosphorylation. Wortmannin had a smaller effect on the activation of MAP kinase by phorbol ester, indicating that phorbol esters may stimulate MAP kinase by a different or additional mechanism to that employed by insulin or serum. Wortmannin had very little effect on the inactivation of GSK-3 by phorbol ester: possible reasons for this are discussed.

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 Glycogen Synthase Kinase 3 Phosphorylates RBL2/p130 during Quiescence

2004 ◽  
Vol 24 (20) ◽  
pp. 8970-8980 ◽  
Author(s):  
Larisa Litovchick ◽  
Anton Chestukhin ◽  
James A. DeCaprio
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Growth Factor Signaling ◽  
Cycle Progression ◽  
Pocket Proteins ◽  
Cyclin Dependent Kinases ◽  
The Stability

ABSTRACT Phosphorylation of the retinoblastoma-related or pocket proteins RB1/pRb, RBL1/p107, and RBL2/p130 regulates cell cycle progression and exit. While all pocket proteins are phosphorylated by cyclin-dependent kinases (CDKs) during the G1/S-phase transition, p130 is also specifically phosphorylated in G0-arrested cells. We have previously identified several phosphorylated residues that match the consensus site for glycogen synthase kinase 3 (GSK3) in the G0 form of p130. Using small-molecule inhibitors of GSK3, site-specific mutants of p130, and phospho-specific antibodies, we demonstrate here that GSK3 phosphorylates p130 during G0. Phosphorylation of p130 by GSK3 contributes to the stability of p130 but does not affect its ability to interact with E2F4 or cyclins. Regulation of p130 by GSK3 provides a novel link between growth factor signaling and regulation of the cell cycle progression and exit.

scholarly journals Mitogen inactivation of glycogen synthase kinase-3β in intact cells via serine 9 phosphorylation

1994 ◽  
Vol 303 (3) ◽  
pp. 701-704 ◽  
Author(s):  
V Stambolic ◽  
J R Woodgett
Keyword(s):  
Cell Fate ◽  
Glycogen Synthase ◽  
Regulatory Proteins ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Serine Kinase ◽  
Intact Cells ◽  
S6 Kinase ◽  
Mitogen Activated Protein

Glycogen synthase kinase-3 (GSK-3), a protein-serine kinase implicated in cell-fate determination and differentiation, phosphorylates several regulatory proteins that are activated by dephosphorylation in response to hormones or growth factors. GSK-3 beta is phosphorylated in vitro at serine 9 by p70 S6 kinase and p90rsk-1, resulting in its inhibition [Sutherland, Leighton, and Cohen (1993) Biochem. J. 296, 15-19]. Using HeLa cells expressing GSK-3 beta or a mutant containing alanine at residue 9, we demonstrate that serine 9 is modified in intact cells and is targeted specifically by p90rsk-1, and that phosphorylation leads to loss of activity. Since p90rsk-1 is directly activated by mitogen-activated protein kinases, agonists of this pathway, such as insulin, repress GSK-3 function.

Glycogen synthase kinase-3 is involved in the regulation of the cell cycle in cerebellar granule cells

2007 ◽  
Vol 53 (2) ◽  
pp. 295-307 ◽  
Author(s):  
M. Yeste-Velasco ◽  
J. Folch ◽  
R. Trullàs ◽  
M.A. Abad ◽  
M. Enguita ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Cerebellar Granule
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