Binding Partner Effect of Binding Effect on Akt Activity References
α-Actinin 4 Essential role in Akt translocation and activation Positive (1)
Androgen Receptor (AR) Forms complex with Akt and Mdm2 which results in AR degradation N/A (2)
APE Associates with the kinase domain of Akt Positive (3)
APPL1 Associates with the kinase domain of Akt Positive (4)
Brk Binds to Akt and limits its activity Negative (5)
cdc25A Forms complex with Akt and Raf1 to promote cell survival Positive (6)
cdc37 Binds to Akt and prevents its degradation Positive (7)
CTMP Binds to the hydrophobic motif of Akt and prevents Akt activation Negative (8)
eNOS Phosphorylation of eNOS at Ser113 and Ser614 disrupts binding to Akt N/A (9)
Ft1 Binds to Akt and increases kinase activity Positive (10)
GRB10 Binds to the PH domain of Akt and potentiates its activation Positive (11)
HSP27 Formation of Akt/HSP27 complex necessary for Akt activation in neutrophils Positive (12)
ILK Phosphorylation of ILK is required for association with Akt and phosphorylation of Ser473 Positive (13)
IRAK2 Associates with Akt and promotes NF-κB activity N/A (14)
JIP1 Interaction with PH domain of Akt1 inhibits JNK activation N/A (15)
p21 Cip1 Binds to Akt2 and causes accumulation of p21 Cip1 in the nucleus and cell cyle exit N/A (16)
Periplakin Binds to the PH domain of Akt and regulates intracellular localization N/A (17)
PIKE-A Binds to Akt and stimulates kinase activity Positive (18)
PP2C A Binds to and dephosphorylates Akt Negative (19)
POSH Binds to Akt2 and downregulates MLK3-JNK activation N/A (20)
Prohibitin 2 Binds to the C-terminus of Akt N/A (21)
Raf1 Akt binds to and phosphorylates Raf1, resulting in decreased Raf1 activity N/A (22)
Smad3 Insulin-induced Akt and Smad3 association blocks Smad3 phosphorylation and nuclear translocation; TGF-β blocks PKB/Smad3 association N/A (23,24)
TCL1 Binds to the PH domain of Akt, forming oligomers, leading to increased Akt activity Positive (25,26)
TRB3 Insulin-mediated association with Akt blocks Akt activation Negative (27)

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

References

  1. Ding, Z. et al. (2006) A retrovirus-based protein complementation assay screen reveals functional AKT1-binding partners. Proc. Natl. Acad. Sci. U.S.A. 103, 15014–15019.
  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 November 2010