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The renaissance of GSK3

Abstract

Glycogen synthase kinase 3 (GSK3) was initially described as a key enzyme involved in glycogen metabolism, but is now known to regulate a diverse array of cell functions. The study of the substrate specificity and regulation of GSK3 activity has been important in the quest for therapeutic intervention.

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Figure 1: The signalling pathway by which insulin inhibits GSK3 and contributes to the stimulation of glycogen and protein synthesis.
Figure 2: The unique substrate specificity of GSK3.
Figure 3: Comparison of the activation loops of GSK3β with the MAPK family member p38γ.
Figure 4: The molecular mechanism by which phosphorylation inhibits GSK3.
Figure 5: Several signalling pathways induce the inhibition of GSK3 by phosphorylating the same serine residue near the amino terminus.
Figure 6: The mechanism by which WNTs prevent the GSK3-catalysed phosphorylation of axin, APC and β-catenin.

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Acknowledgements

Our research is supported by the UK Medical Research Council, Diabetes UK, The Royal Society, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, NovoNordisk and Pfizer. We apologize to the authors whose papers could not be referenced because of space restrictions.

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Correspondence to Philip Cohen.

Supplementary information

Related links

Related links

DATABASES

 FlyBase:

wingless

zeste-white 3

 InterPro:

PH

SH2

 Locuslink:

APC

axin

β-catenin

CDK4

CDK6

c-jun

CK2

c-myc

cyclin D1

DVL

DYRK

eIF2B

FRAT

frizzled

glycogen synthase

GSK3

IGF1

insulin

insulin receptor

IRS1

IRS2

MAPKAP-K1

mTOR

PDK1

6-phosphofructo-1-kinase

PI3K

PKA

PKB

retinoblastoma

S6K

Tau

WNTs

 OMIM:

Alzheimer's disease

NIDDM

 Swiss-Prot:

GBP

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Cohen, P., Frame, S. The renaissance of GSK3. Nat Rev Mol Cell Biol 2, 769–776 (2001). https://doi.org/10.1038/35096075

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