Judging a Protein by More Than Its Name: GSK-3

@article{Woodgett2001JudgingAP,
  title={Judging a Protein by More Than Its Name: GSK-3},
  author={James R. Woodgett},
  journal={Science's STKE},
  year={2001},
  volume={2001},
  pages={re12 - re12}
}
  • J. Woodgett
  • Published 18 September 2001
  • Biology
  • Science's STKE
As knowledge of cellular signal transduction has accumulated, general truisms have emerged, including the notion that signaling proteins are usually activated by stimuli and that they, in turn, mediate the actions of specific agonists. Glycogen synthase kinase-3 (GSK-3) is an unusual protein-serine kinase that bucks these conventions. This evolutionarily conserved protein kinase is active in resting cells and is inhibited in response to activation of several distinct pathways, including those… 
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References

SHOWING 1-10 OF 225 REFERENCES
Selective small-molecule inhibitors of glycogen synthase kinase-3 activity protect primary neurones from death.
TLDR
It is shown that the novel potent and selective small-molecule inhibitors of GSK-3, SB-415286 and SB-216763, protect both central and peripheral nervous system neurones in culture from death induced by reduced PI 3-kinase pathway activity.
Glycogen synthase kinase 3 phosphorylates Jun family members in vitro and negatively regulates their transactivating potential in intact cells.
Expression of immediate-early genes involving the 12-O-tetradecanoyl phorbol 13-acetate (TPA)-responsive element (TRE) is modulated by post-translational modification of pre-existing activator
Selective small‐molecule inhibitors of glycogen synthase kinase‐3 activity protect primary neurones from death
TLDR
The data provide clear pharmacological and biochemical evidence that selective inhibition of the endogenous pool of GSK‐3 activity in primary neurones is sufficient to prevent death, implicating G SK‐3 as a physiologically relevant principal regulatory target of the PI’3‐kinase/PKB neuronal survival pathway.
Suppression of Glycogen Synthase Kinase Activity Is Not Sufficient for Leukemia Enhancer Factor-1 Activation*
TLDR
Investigation of the effect of an activated Akt on the accumulation of cytosolic β-catenin and LEF-1-dependent transcription suggests that inhibition of GSK kinase activity is not sufficient for activation of LEf-1 but may facilitate the activation by reducing the interaction of Gsk for Axin.
Negative regulation of Jun/AP-1: conserved function of glycogen synthase kinase 3 and the Drosophila kinase shaggy.
TLDR
Two forms of GSK-3 function to decrease the DNA-binding activity as well as the transcriptional activation elicited by c-Jun in vivo, and the products of the sgg gene can also function as negative regulators of Jun/AP-1.
Interaction among Gsk-3, Gbp, Axin, and APC in Xenopus Axis Specification
TLDR
GBP functions by preventing the GSK-3–mediated phosphorylation of a protein substrate without eliminating its catalytic activity, and it is shown that APC is impinging upon the canonical Wnt pathway in this model system.
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