Table 1.

Putative GSK-3 substrates

Putative substrateFunctionEffect of phosphorylation by GSK-3References
Kinesin light chainRegulatory component of motor protein involved in vesicular transportInhibits anterograde vesicular movement Morfini et al., 2002
Presenilin 1 (PS1)Transmembrane protein linked to Alzheimer's disease; also binds β-cateninIncreases degradation of C-terminal PS1 fragment Kirschenbaum et al., 2001
TauMicrotubule-associated protein; stabilizes microtubulesReduced microtubule binding; decreased microtubule stability Hanger et al., 1992
β-cateninTranscription transactivatorTargets for degradation Yost et al., 1996
AxinScaffold protein in Wnt PathwayIncreased affinity for β-catenin and increased axin stabilityIkeda et al., 1998; Jho et al., 1999; Yamamoto et al., 1999
Adenomatous Polyposis ColiWnt pathway componentIncreased β-catenin binding; decreased microtubule binding Rubinfeld et al., 1996
TimelessTranscription factor regulating Drosophila circadian rhythmIncreased heterodimerization with clock gene called period or increased nuclear transport suggested Martinek et al., 2001
Nuclear factor of activated T-cells cTranscription factor; early immune response genesDecreased DNA binding; increased nuclear export Beals et al., 1997
Heat shock factor-1Transcription factor; regulates genes in response to potentially lethal stressorsInactivates transcription factor activity Chu et al., 1996
c-JunTranscription factor; component of activator protein-1 (AP-1) that regulates many diverse genesDecreased DNA binding and transactivation Boyle et al., 1991
c-MycTranscription factor; regulates genes involved in cell growth, differentiation and apoptosisTargets for degradationPulverer et al., 1994; Sears et al., 2000
cAMP response element binding proteinTranscription factor; regulates cAMP-responsive genesIncreased transcription factor activity Fiol et al., 1994
Microphthalmia-associated transcription factorTranscription factor; regulates tyrosinase expressionIncreased binding to tyrosinase promoterKhaled et al., 2002; Takeda et al., 2000
Cylin D1Transcription factor; cell cycle regulationIncreased nuclear export; targets for degradation Diehl et al., 1998
eIF-2B translation factorCritical for translation initiationInhibits activitySingh et al., 1996; Welsh and Proud, 1993
Inhibitor-2Regulatory subunit of phosphataseActivates phosphatase Park et al., 1994
Glycogen synthaseGlycogen metabolismInhibits enzyme activityDent et al., 1989; Dent et al., 1990; Fiol et al., 1988
Insulin receptor substrate 1Insulin signallingInhibits insulin receptor signalling Eldar-Finkelman and Krebs, 1997
Acetyl CoA carboxylaseKey lipogenic enzymeInactivates enzyme Hughes et al., 1992
ATP-citrate lyaseFatty acid synthesisInactivates enzymeBenjamin et al., 1994; Hughes et al., 1992
Mucin 1/DF3 antigenTransmembrane glycoprotein that binds β-catenin; overexpressed in human carcinomasDecreases interaction with β-catenin Li et al., 1998
  • Substrates involved in Alzheimer's disease are shaded blue, components of the Wnt pathway are shaded yellow, transcription factors are shaded green and proteins involved in protein, insulin and lipid metabolism are shaded red.