Putative GSK-3 substrates
| Putative substrate . | Function . | Effect of phosphorylation by GSK-3 . | References . |
|---|---|---|---|
| Kinesin light chain | Regulatory component of motor protein involved in vesicular transport | Inhibits anterograde vesicular movement | Morfini et al., 2002 |
| Presenilin 1 (PS1) | Transmembrane protein linked to Alzheimer's disease; also binds β-catenin | Increases degradation of C-terminal PS1 fragment | Kirschenbaum et al., 2001 |
| Tau | Microtubule-associated protein; stabilizes microtubules | Reduced microtubule binding; decreased microtubule stability | Hanger et al., 1992 |
| β-catenin | Transcription transactivator | Targets for degradation | Yost et al., 1996 |
| Axin | Scaffold protein in Wnt Pathway | Increased affinity for β-catenin and increased axin stability | Ikeda et al., 1998; Jho et al., 1999; Yamamoto et al., 1999 |
| Adenomatous Polyposis Coli | Wnt pathway component | Increased β-catenin binding; decreased microtubule binding | Rubinfeld et al., 1996 |
| Timeless | Transcription factor regulating Drosophila circadian rhythm | Increased heterodimerization with clock gene called period or increased nuclear transport suggested | Martinek et al., 2001 |
| Nuclear factor of activated T-cells c | Transcription factor; early immune response genes | Decreased DNA binding; increased nuclear export | Beals et al., 1997 |
| Heat shock factor-1 | Transcription factor; regulates genes in response to potentially lethal stressors | Inactivates transcription factor activity | Chu et al., 1996 |
| c-Jun | Transcription factor; component of activator protein-1 (AP-1) that regulates many diverse genes | Decreased DNA binding and transactivation | Boyle et al., 1991 |
| c-Myc | Transcription factor; regulates genes involved in cell growth, differentiation and apoptosis | Targets for degradation | Pulverer et al., 1994; Sears et al., 2000 |
| cAMP response element binding protein | Transcription factor; regulates cAMP-responsive genes | Increased transcription factor activity | Fiol et al., 1994 |
| Microphthalmia-associated transcription factor | Transcription factor; regulates tyrosinase expression | Increased binding to tyrosinase promoter | Khaled et al., 2002; Takeda et al., 2000 |
| Cylin D1 | Transcription factor; cell cycle regulation | Increased nuclear export; targets for degradation | Diehl et al., 1998 |
| eIF-2B translation factor | Critical for translation initiation | Inhibits activity | Singh et al., 1996; Welsh and Proud, 1993 |
| Inhibitor-2 | Regulatory subunit of phosphatase | Activates phosphatase | Park et al., 1994 |
| Glycogen synthase | Glycogen metabolism | Inhibits enzyme activity | Dent et al., 1989; Dent et al., 1990; Fiol et al., 1988 |
| Insulin receptor substrate 1 | Insulin signalling | Inhibits insulin receptor signalling | Eldar-Finkelman and Krebs,1997 |
| Acetyl CoA carboxylase | Key lipogenic enzyme | Inactivates enzyme | Hughes et al., 1992 |
| ATP-citrate lyase | Fatty acid synthesis | Inactivates enzyme | Benjamin et al., 1994; Hughes et al., 1992 |
| Mucin 1/DF3 antigen | Transmembrane glycoprotein that binds β-catenin; overexpressed in human carcinomas | Decreases interaction with β-catenin | Li et al., 1998 |
| Putative substrate . | Function . | Effect of phosphorylation by GSK-3 . | References . |
|---|---|---|---|
| Kinesin light chain | Regulatory component of motor protein involved in vesicular transport | Inhibits anterograde vesicular movement | Morfini et al., 2002 |
| Presenilin 1 (PS1) | Transmembrane protein linked to Alzheimer's disease; also binds β-catenin | Increases degradation of C-terminal PS1 fragment | Kirschenbaum et al., 2001 |
| Tau | Microtubule-associated protein; stabilizes microtubules | Reduced microtubule binding; decreased microtubule stability | Hanger et al., 1992 |
| β-catenin | Transcription transactivator | Targets for degradation | Yost et al., 1996 |
| Axin | Scaffold protein in Wnt Pathway | Increased affinity for β-catenin and increased axin stability | Ikeda et al., 1998; Jho et al., 1999; Yamamoto et al., 1999 |
| Adenomatous Polyposis Coli | Wnt pathway component | Increased β-catenin binding; decreased microtubule binding | Rubinfeld et al., 1996 |
| Timeless | Transcription factor regulating Drosophila circadian rhythm | Increased heterodimerization with clock gene called period or increased nuclear transport suggested | Martinek et al., 2001 |
| Nuclear factor of activated T-cells c | Transcription factor; early immune response genes | Decreased DNA binding; increased nuclear export | Beals et al., 1997 |
| Heat shock factor-1 | Transcription factor; regulates genes in response to potentially lethal stressors | Inactivates transcription factor activity | Chu et al., 1996 |
| c-Jun | Transcription factor; component of activator protein-1 (AP-1) that regulates many diverse genes | Decreased DNA binding and transactivation | Boyle et al., 1991 |
| c-Myc | Transcription factor; regulates genes involved in cell growth, differentiation and apoptosis | Targets for degradation | Pulverer et al., 1994; Sears et al., 2000 |
| cAMP response element binding protein | Transcription factor; regulates cAMP-responsive genes | Increased transcription factor activity | Fiol et al., 1994 |
| Microphthalmia-associated transcription factor | Transcription factor; regulates tyrosinase expression | Increased binding to tyrosinase promoter | Khaled et al., 2002; Takeda et al., 2000 |
| Cylin D1 | Transcription factor; cell cycle regulation | Increased nuclear export; targets for degradation | Diehl et al., 1998 |
| eIF-2B translation factor | Critical for translation initiation | Inhibits activity | Singh et al., 1996; Welsh and Proud, 1993 |
| Inhibitor-2 | Regulatory subunit of phosphatase | Activates phosphatase | Park et al., 1994 |
| Glycogen synthase | Glycogen metabolism | Inhibits enzyme activity | Dent et al., 1989; Dent et al., 1990; Fiol et al., 1988 |
| Insulin receptor substrate 1 | Insulin signalling | Inhibits insulin receptor signalling | Eldar-Finkelman and Krebs,1997 |
| Acetyl CoA carboxylase | Key lipogenic enzyme | Inactivates enzyme | Hughes et al., 1992 |
| ATP-citrate lyase | Fatty acid synthesis | Inactivates enzyme | Benjamin et al., 1994; Hughes et al., 1992 |
| Mucin 1/DF3 antigen | Transmembrane glycoprotein that binds β-catenin; overexpressed in human carcinomas | Decreases 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.