Reactome | Activated AKT phosphorylates AKT1S1 (PRAS40)

Activated AKT phosphorylates AKT1S1 (PRAS40)

Stable Identifier

R-HSA-377186

Type

Reaction [transition]

Species

Homo sapiens

Compartment

lysosomal membrane, cytosol

ReviewStatus

4/5

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Activated AKT phosphorylates AKT1S1 (PRAS40)

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AKT1 phosphorylates AKT1S1 (PRAS40, Proline Rich Akt Substrate 40 kDa) at Thr-246 (Kovacina et al. 2003; Sancak et al. 2007; Oshiro et al. 2007; Vander Haar et al. 2007; Wang et al. 2008; Mi et al. 2015). AKT1S1 is an inhibitory accessory protein of mTORC1. Phosphorylation of AKT1S1 by AKT releases the inhibition of mTORC1.

Mice engineered to express AKT1S1 T246A mutant in the basal keratinocytes of epidermis are resistant to epidermal tumorigenesis induced by the treatment with the tumor promoter TPA (12-O-tetradecanoyl-phorbol-13-acetate) and show persistent association of AKT1S1 T246A with the mTORC1 complex, even under mTOR signaling activating conditions (Rho et al. 2016).

AKT2 also phosphorylates AKT1S1 (Kovacina et al. 2003; Quambusch et al. 2021), as does AKT3 (Madhunapantula et al. 2007; Sun et al. 2020).

Literature References

PubMed ID	Title	Journal	Year
31692069	M2-polarized tumor-associated macrophages promote epithelial-mesenchymal transition via activation of the AKT3/PRAS40 signaling pathway in intrahepatic cholangiocarcinoma Sun, D, Luo, T, Dong, P, Zhang, N, Chen, J, Zhang, S, Dong, L, Janssen, HLA, Zhang, S	J Cell Biochem	2020
17517883	The proline-rich Akt substrate of 40 kDa (PRAS40) is a physiological substrate of mammalian target of rapamycin complex 1 Oshiro, N, Takahashi, R, Yoshino, K, Tanimura, K, Nakashima, A, Eguchi, S, Miyamoto, T, Hara, K, Takehana, K, Avruch, J, Kikkawa, U, Yonezawa, K	J Biol Chem	2007
18372248	Regulation of proline-rich Akt substrate of 40 kDa (PRAS40) function by mammalian target of rapamycin complex 1 (mTORC1)-mediated phosphorylation Wang, L, Harris, TE, Lawrence JC, Jr	J Biol Chem	2008
34489430	Cellular model system to dissect the isoform-selectivity of Akt inhibitors Quambusch, L, Depta, L, Landel, I, Lubeck, M, Kirschner, T, Nabert, J, Uhlenbrock, N, Weisner, J, Kostka, M, Levy, LM, Schultz-Fademrecht, C, Glanemann, F, Althoff, K, Müller, MP, Siveke, JT, Rauh, D	Nat Commun	2021
12524439	Identification of a proline-rich Akt substrate as a 14-3-3 binding partner Kovacina, KS, Park, GY, Bae, SS, Guzzetta, AW, Schaefer, E, Birnbaum, MJ, Roth, RA	J Biol Chem	2003
17440074	PRAS40 deregulates apoptosis in malignant melanoma Madhunapantula, SV, Sharma, A, Robertson, GP	Cancer Res	2007
25961827	AKT inhibition overcomes rapamycin resistance by enhancing the repressive function of PRAS40 on mTORC1/4E-BP1 axis Mi, W, Ye, Q, Liu, S, She, QB	Oncotarget	2015
17277771	Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40 Vander Haar, E, Lee, SI, Bandhakavi, S, Griffin, TJ, Kim, DH	Nat Cell Biol	2007
17386266	PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase Sancak, Y, Thoreen, CC, Peterson, TR, Lindquist, RA, Kang, SA, Spooner, E, Carr, SA, Sabatini, DM	Mol Cell	2007