Binding Partner Effect of Binding Effect on Akt Activity References
GAPDH Binds to active Akt and limits its dephosphorylation Positive Jacquin, M.A. et al. (2013) Cell Death Differ. 20, 1043–1054.
Jade-1 Binds to and inhibits Akt kinase activity Negative Zeng, L. et al. (2013) Cancer Res. 73, 5371–5380.
Mst1 Binds to and inhibits Akt kinase activity Negative Cinar, B. et al. (2007) EMBO J. 26, 4523–4534.
Jang, S.W. et al. (2007) J. Biol. Chem. 282, 30836–30844.
ArgBP2γ Binds and functions as an adaptor for Akt and PAK1 N/A Yuan, Z.Q. et al. (2005) J. Biol. Chem. 280, 21483–21490.
CBP Akt binds and phosphorylates CBP to regulate CBP activity N/A Liu, Y. et al. (2013) FEBS Lett. 587, 847–853.
PP1 Binds Akt and dephosphorylates Akt at Thr450 Negative Xiao, L. et al. (2010) Cell Death Differ. 17, 1448–1462.
PLCγ1 Akt binds and phosphorylates PLCγ1 N/A Wang, Y. et al. (2006) Mol. Biol. Cell 17, 2267–2277.
Skp2 Akt binds and phosphorylates Skp2 to regulate Skp2 activity N/A Lin, H. et al. (2009) Nat. Cell Biol. 11, 420–432.
Gao, D. et al. (2009) Nat. Cell Biol. 11, 397–408
PEA-15 Akt binds and phosphorylates PEA-15 to regulate its anti-apoptotic function. N/A Trencia, A. et al. (2003) Cell. Biol. 23, 4511–4521.
PHF20 Akt binds and phosphorylates PHF20 to regulate its subcellular localization N/A Park, S. et al. (2012) J. Biol. Chem. 287, 11151–11163.
PHLPP PHLPP binds Akt and dephosphorylates Akt at Ser473 Negative Gao, T. et al. Mol. Cell 18, 13–24.
FKBP5 Binds Akt and acts as a scaffold for the interaction of Akt with PHLPP Negative Pei, H. et al. (2009) Cancer Cell 16, 259–266.
CKIP-1 Binds Akt and inhibits Akt phosphorylation Negative Tokuda, E. et al. (2007) Cancer Res. 67, 9666–9676.
Ras Interacts with the pleckstrin homology domain of Akt Positive Yue, Y. et al. (2004) J. Biol. Chem. 279, 12883–12889.
BTBD10 Binds Akt and inhibits its dephosphorylation Positive Nawa, M. et al. (2008) Cell Signal. 20, 493–505.
KCTD20 Binds Akt and inhibits its dephosphorylation Positive Nawa, M. et al. (2013) BMC Biochem. 14, 27.
PAR-4 Akt binds and phosphorylates PAR-4 to inhibit its pro-apoptotic activity N/A Goswami, A. et al. (2005) Mol. Cell 20, 33–44.
Tpl2 Akt binds and phosphorylates Tpl2 N/A Kane, L.P. et al. (2002) Mol. Cell. Biol. 22, 5962–5974.
SirT2 SirT2 interacts with Akt and is required for optimal Akt activation Positive Ramakrishnan, G. et al. (2014) J. Biol. Chem. 289, 6054–6066.
NPM Binds the pleckstrin homology domain of Akt to promote cell survival N/A Lee, S.B. et al. (2008) Proc. Natl. Acad. Sci. USA 105, 16584–16589.
Kwon, I.S. et al. (2010) BMB Rep. 43, 127–132.
eEF1A Interacts with Akt and contributes to Akt phosphorylation Positive Pecorari, L. et al. (2009) Mol. Cancer 8, 58.
CLIPR-59 Interacts with the kinase domain of Akt and regulates the subcellular localization of Akt N/A Ding, J. et al. (2009) Mol. Cell. Biol. 29, 1459–1471.
CNK1 Binds and enhances Akt activation Positive Fritz, R.D. et al. (2010) Oncogene 29, 3575–3582.
Phafin2 Binds Akt in the lysosome to regulate autophagy N/A Matsuda–Lennikov, M. et al. (2014) PLoS One 9, e79795.
Btk Binds Akt and promotes Akt phosphorylation Positive Lindvall, J. et al. (2002) Biochem. Biophys. Res. Commun. 293, 1319–1326.
β-Parvin Binds Akt and prevents the interaction of Akt with ILK Negative Kimura, M. et al. (2010) J. Cell Sci. 123, 747–755.
NS1 Interacts with the pleckstrin homology domain of Akt Positive Matsuda, M. et al. (2010) Biochem. Biophys. Res. Commun. 395, 312–317.
α-Synuclein Binds Akt and promotes Akt activation Positive Chung, J.Y. et al. (2011) Neurosignals 19, 86–96.
RACK1 RACK1 interacts with Akt in a complex with PP2A Negative Li, G. et al. (2012) Nat. Commun. 3, 667.
ProF Binds Akt and influences the subcellular localization of Akt N/A Fritzius, T. et al. (2006) Biochem. J. 399, 9–20.
p27 Kip1 Akt binds and phosphorylates p27 N/A Liang, J. et al. (2002) Nat. Med. 8, 1153–1160.
Shin, I. et al. (2002) Nat. Med. 8, 1145–1152.
FoxA2/HNF3β Akt binds and phosphorylates FoxA2/HNF3β N/A Wolfrum, C. et al. (2003) Proc. Natl. Acad. Sci. USA 100, 11624–11629.
DNMT1 Akt binds and phosphorylates DNMT1 N/A Estève, P.O. et al. (2011) Nat. Struct. Mol. Biol. 18, 42–48.

CST would like to thank Prof. Michael Scheid, York University, Toronto, Ontario for creating this table.

References

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  2. Lin, H.K. et al. (2002) Phosphorylation-dependent ubiquitylation and degradation of androgen receptor by Akt require Mdm2 E3 ligase. EMBO J. 21, 4037–4048.
  3. Anai, M. et al. (2005) A novel protein kinase B (PKB)/AKT-binding protein enhances PKB kinase activity and regulates DNA synthesis. J. Biol. Chem. 280, 18525–18535.
  4. Mitsuuchi, Y. et al. (1999) Identification of a chromosome 3p14.3-21.1 gene, APPL, encoding an adaptor molecule that interacts with the oncoprotein-serine/threonine kinase AKT2. Oncogene 18, 4891–4898.
  5. Zhang, P. et al. (2005) Regulated association of protein kinase B/Akt with breast tumor kinase. J. Biol. Chem. 280, 1982–1991.
  6. Fuhrmann, G. et al. (2001) Cdc25A phosphatase suppresses apoptosis induced by serum deprivation. Oncogene 20, 4542–4553.
  7. Miyata, Y. et al. (2004) CK2 controls multiple protein kinases by phosphorylating a kinase-targeting molecular chaperone, Cdc37. Mol. Cell. Biol. 24, 4065–4074.
  8. Maira, S.M. et al. (2001) Carboxyl-terminal modulator protein (CTMP), a negative regulator of PKB/Akt and v-Akt at the plasma membrane. Science 294, 374–380.
  9. Bauer, P.M. et al. (2003) Compensatory phosphorylation and protein-protein interactions revealed by loss of function and gain of function mutants of multiple serine phosphorylation sites in endothelial nitric-oxide synthase. J. Biol. Chem. 278, 14841–14849.
  10. Remy, I. et al. (2004) Regulation of apoptosis by the Ft1 protein, a new modulator of protein kinase B/Akt. Mol. Cell. Biol. 24, 1493–1504.
  11. Jahn, T. et al. (2002) Role for the adaptor protein Grb10 in the activation of Akt. Mol. Cell. Biol. 22, 979–991.
  12. Rane, M.J. et al. (2003) Heat shock protein 27 controls apoptosis by regulating Akt activation. J. Biol. Chem. 278, 27828–27835.
  13. Persad, S. et al. (2001) Regulation of protein kinase B/Akt-serine 473 phosphorylation by integrin-linked kinase: critical roles for kinase activity and amino acids arginine 211 and serine 343. J. Biol. Chem. 276, 27462–27469.
  14. Cenni, V. et al. (2003) Interleukin-1-receptor-associated kinase 2 (IRAK2)-mediated interleukin-1-dependent nuclear factor kappaB transactivation in Saos2 cells requires the Akt/protein kinase B kinase. Biochem. J. 376, 303–311.
  15. Kim, A.H. et al. (2002) Akt1 regulates a JNK scaffold during excitotoxic apoptosis. Neuron 35, 697–709.
  16. Héron-Milhavet, L. et al. (2006) Only Akt1 is required for proliferation, while Akt2 promotes cell cycle exit through p21 binding. Mol. Cell. Biol. 26, 8267–8280.
  17. van den Heuvel, A.P. et al. (2002) Binding of protein kinase B to the plakin family member periplakin. J. Cell. Sci. 115, 3957–3966.
  18. Ahn, J.Y. et al. (2004) PIKE (phosphatidylinositol 3-kinase enhancer)-A GTPase stimulates Akt activity and mediates cellular invasion. J. Biol. Chem. 279, 16441–16451.
  19. Pim, D. et al. (2005) Activation of the protein kinase B pathway by the HPV-16 E7 oncoprotein occurs through a mechanism involving interaction with PP2A. Oncogene 24, 7830–7838.
  20. Figueroa, C. et al. (2003) Akt2 negatively regulates assembly of the POSH-MLK-JNK signaling complex. J. Biol. Chem. 278, 47922–47927.
  21. Sun, L. et al. (2004) Akt binds prohibitin 2 and relieves its repression of MyoD and muscle differentiation. J. Cell. Sci. 117, 3021–3029.
  22. Reusch, H.P. et al. (2001) Regulation of Raf by Akt controls growth and differentiation in vascular smooth muscle cells. J. Biol. Chem. 276, 33630–33637.
  23. Conery, A.R. et al. (2004) Akt interacts directly with Smad3 to regulate the sensitivity to TGF-beta induced apoptosis. Nat. Cell Biol. 6, 366–372.
  24. Remy, I. et al. (2004) PKB/Akt modulates TGF-beta signalling through a direct interaction with Smad3. Nat. Cell Biol. 6, 358–365.
  25. Laine, J. et al. (2000) The protooncogene TCL1 is an Akt kinase coactivator. Mol. Cell 6, 395–407.
  26. Pekarsky, Y. et al. (2000) Tcl1 enhances Akt kinase activity and mediates its nuclear translocation. Proc. Natl. Acad. Sci. U.S.A. 97, 3028–3033.
  27. Du, K. et al. (2003) TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver. Science 300, 1574–1577.

created September 2007

revised September 2014