PI3K / Akt Binding Partners
|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.
- 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.
- 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.
- 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.
- 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.
- Zhang, P. et al. (2005) Regulated association of protein kinase B/Akt with breast tumor kinase. J. Biol. Chem. 280, 1982–1991.
- Fuhrmann, G. et al. (2001) Cdc25A phosphatase suppresses apoptosis induced by serum deprivation. Oncogene 20, 4542–4553.
- Miyata, Y. et al. (2004) CK2 controls multiple protein kinases by phosphorylating a kinase-targeting molecular chaperone, Cdc37. Mol. Cell. Biol. 24, 4065–4074.
- 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.
- 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.
- 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.
- Jahn, T. et al. (2002) Role for the adaptor protein Grb10 in the activation of Akt. Mol. Cell. Biol. 22, 979–991.
- Rane, M.J. et al. (2003) Heat shock protein 27 controls apoptosis by regulating Akt activation. J. Biol. Chem. 278, 27828–27835.
- 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.
- 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.
- Kim, A.H. et al. (2002) Akt1 regulates a JNK scaffold during excitotoxic apoptosis. Neuron 35, 697–709.
- 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.
- 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.
- 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.
- 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.
- Figueroa, C. et al. (2003) Akt2 negatively regulates assembly of the POSH-MLK-JNK signaling complex. J. Biol. Chem. 278, 47922–47927.
- Sun, L. et al. (2004) Akt binds prohibitin 2 and relieves its repression of MyoD and muscle differentiation. J. Cell. Sci. 117, 3021–3029.
- 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.
- 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.
- Remy, I. et al. (2004) PKB/Akt modulates TGF-beta signalling through a direct interaction with Smad3. Nat. Cell Biol. 6, 358–365.
- Laine, J. et al. (2000) The protooncogene TCL1 is an Akt kinase coactivator. Mol. Cell 6, 395–407.
- 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.
- 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