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AKT1 phosphorylates AKT1S1 (PRAS40, Proline Rich Akt Subs... Show undefined attributes

created	[InstanceEdit:377173] Williams, MG, 2008-09-12 10:01:25
dbId	376995
displayName	AKT1 phosphorylates AKT1S1 (PRAS40, Proline Rich Akt Subs...
literatureReference	[LiteratureReference:9975231] AKT inhibition overcomes rapamycin resistance by enhancing the repressive function of PRAS40 on mTORC1/4E-BP1 axis [LiteratureReference:377264] PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase [LiteratureReference:200154] Identification of a proline-rich Akt substrate as a 14-3-3 binding partner [LiteratureReference:377225] The proline-rich Akt substrate of 40 kDa (PRAS40) is a physiological substrate of mammalian target of rapamycin complex 1 [LiteratureReference:200166] Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40 [LiteratureReference:377103] Regulation of proline-rich Akt substrate of 40 kDa (PRAS40) function by mammalian target of rapamycin complex 1 (mTORC1)-mediated phosphorylation [LiteratureReference:9975229] Overexpression of PRAS40(T246A) in the Proliferative Compartment Suppresses mTORC1 Signaling, Keratinocyte Migration, and Skin Tumor Development [LiteratureReference:9975665] Cellular model system to dissect the isoform-selectivity of Akt inhibitors [LiteratureReference:9975654] M2-polarized tumor-associated macrophages promote epithelial-mesenchymal transition via activation of the AKT3/PRAS40 signaling pathway in intrahepatic cholangiocarcinoma
modified	[InstanceEdit:9982496] Orlic-Milacic, Marija, 2026-02-18
schemaClass	Summation
text	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).

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[Reaction:R-HSA-377186] Activated AKT phosphorylates AKT1S1 (PRAS40)

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