Table 1. Direct AMPK Targets.
List of previously validated direct targets of AMPK.
| AMPK Target | Target Site (Human) | Functional Consequence | References |
|---|---|---|---|
| ACC1 | S80 | Inhibits ACC enzymatic activity leading to inhibition of de novo lipogenesis | Carlson & Kim (1973), Davies et al. (1990), Ha et al. (1994), Munday et al. (1988) |
| ACC2 | S222 | Inhibits ACC enzymatic activity leading to promotion of fatty acid oxidation | Winder et al. (1997), Chen et al. (2000), Dzamko et al. (2008), Steinberg et al. (2010) |
| AKAP1 | S107 | Facilitates mitochondrial respiration | Hoffman et al. (2015) |
| AMOTL1 | S793 | AMPK phosphorylates AMOTL1 to stimulate Lats kinase which inhibits YAP | DeRan et al. (2014) |
| Beclin-1 | S91, S94 | Induces autophagy | Kim et al. (2013) |
| BRAF | S729 | Promotes the association of BRAF with 14-3-3 proteins and disrupts its interaction with the KSR1 scaffolding protein | Shen et al. (2013) |
| CKIe (Clock) | S389 | Increases CKIe activity | Um et al. (2007) |
| CLIP-170 | S312 | Results in CLIP-170 localizing closer to the distal end of the microtubules (cell polarity), modulating cell migration | Nakano & Takashima (2010) |
| CREB | S133 | Increases CREB transcriptional activity and expression of downstream target genes | Thomson et al. (2008) |
| CRY1 Clock) | S71 | Targets CRY1 toward ubiquitin mediated degradation | Lamia et al. (2009) |
| CRTC2/TORC2 | S171 | Induces 14-3-3- interaction, blocks nuclear translocation and association/activation of CREB | Koo et al. (2005) |
| eEF2K | S398 | Activates eEF2K and blocks translation elongation by inactivating eEF2; can also induce autophagy | Browne et al. (2004), Hong-Brown et al. (2008), Leprivier et al. (2013), Xie et al. (2014) |
| FOXO3 | S413, S588 | Increases transcriptional activity of FOXO3 | Greer et al. (2007), Bodur et al. (2015) |
| GBF1 | T1337 | Suppresses GEF activity of GBF1 resulting in disassembly of the Golgi apparatus | Miyamoto et al. (2008) |
| GFAT1/GFPT1 | S261 | Inhibits enzymatic activity of GFAT1, decreasing flux through the hexosamine biosynthetic pathway | Li et al. (2007), Eguchi et al. (2009) |
| HDAC4/5/7 | S259, S498 | Induces 14-3-3 binding, cytoplasmic sequestration and inhibition of HDACs | McGee et al. (2008), Mihaylova et al. (2011) |
| H2B | S37 | Increases transcription of genes involved in cell survival | Bungard et al. (2010), |
| HMGCR | S872 | Inactivates HMGCR and thus inhibits cholesterol synthesis | Clarke & Hardie (1990) |
| HNF4 | S304 | Represses transcriptional activity of HNF4α | Hong et al. (2003) |
| IRS1 | S794 | Context-dependent regulation of PI3K-Akt signaling | Jakobsen et al. (2001), Qiao et al. (2002), Tzatsos et al. (2007) |
| MFF | S155, S172 | Induction of mitochondrial fission | Toyama et al. (2016), Ducommun et al. (2015) |
| PAK2 | S20 | Promotes PAK2 activity, leading to increased phosphorylation/inhibition of MRLC | Banko et al. (2011) |
| PFKFB2 | S466 | Increases PFKFB2 kinase activity and glycolysis | Marsin et al (2000) |
| PFKFB3 | S461 | Increases PFKFB3 kinase activity and glycolysis | Marsin et al (2002) |
| p27 | T198 | Stabilizes p27, inducing autophagy-mediated cell survival | Liang et al. (2007) |
| p300 | S89 | Inhibits its ability to interact with nuclear receptors | Leff et al. (2003), Yang et al. (2001) |
| p53 | S15 | Increases p53 activity, promotes expression of p21 and cell cycle arrest | Imamura et al. (2001), Jones et al. (2005) |
| PGC-1α | T177, S538 | Induction of PGC-1α and mitochondrial biogenesis | Jager et al. (2007) |
| PPP1R12C | S452 | Induces 14-3-3 binding and inhibition of PPP1R12C, leading to increased phosphorylation/inhibition of MRLC | Banko et al. (2011) |
| Rb | S811 | Inhibition of Rb followed by subsequent increased proliferation | Dasgupta et al. (2009), Rios et al. (2013) |
| RPTOR | S722, S792 | Induces 14-3-3 binding and inhibition of mTOR | Gwinn, D.M., et al. (2008) |
| SIRT1 | T344 | Disrupts the interaction between SIRT1 and its inhibitor DBC1 | Lau et al. (2014) |
| SREBP1 | S396 | Inhibits transcriptional activity of SREBP1 | Li et al. (2011) |
| TBC1D1 | S237, T596 | Promotes 14-3-3 binding and glucose transporter (ex. GLUT4) trafficking | Chen et al. (2008), Chavez et al. (2008), Pehmoller et al. (2009) |
| TBC1D4/AS160 | T642, S704 | Promotes 14-3-3 binding and glucose transporter (ex. GLUT4) trafficking | Treebak et al. (2006), Kramer et al. (2006), Treebak et al. (2010) |
| TSC2 | T1227, S1345 | Enhances TSC2 activity | Inoki et al (2003) |
| ULK1 | S317, S467, S556, S778 | Activates ULK1, promotes autophagy | Kim et al. (2011), Egan et al. (2011) |
| VPS34 | T163/S165 | Inhibits the non-autophagy Vps34 complex | Kim et al. (2013) |
| YAP | S94 | Disrupts YAP-TEAD interaction and leads to inhibition of YAP | Mo et al. (2014) |