Cell Signaling Technology

Akt Binding Partners

Akt interacting proteins

Akt interacting proteins. Proteins that promote Akt activation are shown in green, while proteins that inhibit Akt activation are shown in red.

Binding Partner Function Net effect on Akt activity Reference
CTMP Binds to the hydrophobic motif of Akt and prevents Akt activation. Negative (1)
Ft1 Binds to Akt and increases kinase activity. Positive (2)
Periplakin Binds to the PH domain of Akt and regulates intracellular localization. N/A (3)
POSH Akt2 binding with POSH downregulates MLK3-JNK activation. N/A (4)
Smad3 Insulin-induced Akt and Smad3 association blocks Smad3 phosphorylation and nuclear translocation. TGF-β blocks PKB/Smad3 association. N/A (5,6)
TCL1 Binds to the PH domain of Akt, forming oligomers, leading to increased Akt activity. Positive (7,8)
TRB3 Insulin-mediated association with Akt blocks Akt activation. Negative (9)
α-Actinin 4 Essential role in Akt translocation and activation. Positive (10)
JIP1 Interaction with PH domain of Akt1 inhibits JNK activation. N/A (11)
GRB10 Binds to the PH domain of Akt and potentiates its activation. Positive (12)
APPL1 Associates with the kinase domain of Akt. Positive (13)
APE Associates with the kinase domain of Akt. Positive (14)
Prohibitin 2 Binds to the C-terminus of Akt. N/A (15)

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

References

  1. Maira SM, Galetic I, Brazil DP, Kaech S, Ingley E, Thelen M, Hemmings BA (2001) Carboxyl-terminal modulator protein (CTMP), a negative regulator of PKB/Akt and v-Akt at the plasma membrane. Science 294(5541), 374–80.
  2. Remy I, Michnick SW (2004) Regulation of apoptosis by the Ft1 protein, a new modulator of protein kinase B/Akt. Mol. Cell. Biol. 24(4), 1493–504.
  3. van den Heuvel AP, de Vries-Smits AM, van Weeren PC, Dijkers PF, de Bruyn KM, Riedl JA, Burgering BM (2002) Binding of protein kinase B to the plakin family member periplakin. J. Cell. Sci. 115(Pt 20), 3957–66.
  4. Figueroa C, Tarras S, Taylor J, Vojtek AB (2003) Akt2 negatively regulates assembly of the POSH-MLK-JNK signaling complex. J. Biol. Chem. 278(48), 47922–7.
  5. Conery AR, Cao Y, Thompson EA, Townsend CM, Ko TC, Luo K (2004) Akt interacts directly with Smad3 to regulate the sensitivity to TGF-beta induced apoptosis. Nat. Cell Biol. 6(4), 366–72.
  6. Remy I, Montmarquette A, Michnick SW (2004) PKB/Akt modulates TGF-beta signalling through a direct interaction with Smad3. Nat. Cell Biol. 6(4), 358–65.
  7. Laine J, Künstle G, Obata T, Sha M, Noguchi M (2000) The protooncogene TCL1 is an Akt kinase coactivator. Mol. Cell 6(2), 395–407.
  8. Pekarsky Y, Koval A, Hallas C, Bichi R, Tresini M, Malstrom S, Russo G, Tsichlis P, Croce CM (2000) Tcl1 enhances Akt kinase activity and mediates its nuclear translocation. Proc. Natl. Acad. Sci. U.S.A. 97(7), 3028–33.
  9. Du K, Herzig S, Kulkarni RN, Montminy M (2003) TRB3: a tribbles homolog that inhibits Akt/PKB activation by insulin in liver. Science 300(5625), 1574–7.
  10. Ding Z, Liang J, Lu Y, Yu Q, Songyang Z, Lin SY, Mills GB (2006) A retrovirus-based protein complementation assay screen reveals functional AKT1-binding partners. Proc. Natl. Acad. Sci. U.S.A. 103(41), 15014–9.
  11. Kim AH, Yano H, Cho H, Meyer D, Monks B, Margolis B, Birnbaum MJ, Chao MV (2002) Akt1 regulates a JNK scaffold during excitotoxic apoptosis. Neuron 35(4), 697–709.
  12. Jahn T, Seipel P, Urschel S, Peschel C, Duyster J (2002) Role for the adaptor protein Grb10 in the activation of Akt. Mol. Cell. Biol. 22(4), 979–91.
  13. Mitsuuchi Y, Johnson SW, Sonoda G, Tanno S, Golemis EA, Testa JR (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(35), 4891–8.
  14. Anai M, Shojima N, Katagiri H, Ogihara T, Sakoda H, Onishi Y, Ono H, Fujishiro M, Fukushima Y, Horike N, Viana A, Kikuchi M, Noguchi N, Takahashi S, Takata K, Oka Y, Uchijima Y, Kurihara H, Asano T (2005) A novel protein kinase B (PKB)/AKT-binding protein enhances PKB kinase activity and regulates DNA synthesis. J. Biol. Chem. 280(18), 18525–35.
  15. Sun L, Liu L, Yang XJ, Wu Z (2004) Akt binds prohibitin 2 and relieves its repression of MyoD and muscle differentiation. J. Cell. Sci. 117(Pt 14), 3021–9.

revised May 2007

Reference