PI3K / Akt Binding Partners Table
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
- 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 September 2014