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Details on Person Constitutively active AKT isoforms, AKT1, AKT2 and AKT3, wer...
| Class:Id | Summation:9986784 |
|---|---|
| _displayName | Constitutively active AKT isoforms, AKT1, AKT2 and AKT3, wer... |
| _timestamp | 2026-04-06 15:33:38 |
| created | [InstanceEdit:9986786] Orlic-Milacic, Marija, 2026-04-06 |
| literatureReference | [LiteratureReference:9986785] Down-regulation of Notch-dependent transcription by Akt in vitro [LiteratureReference:9604316] AKT and 14-3-3 regulate Notch4 nuclear localization [LiteratureReference:9986822] AKT1-Mediated NOTCH1 phosphorylation promotes gastric cancer progression via targeted regulation of IRS-1 transcription [LiteratureReference:9986808] Pten coordinates retinal neurogenesis by regulating Notch signalling [LiteratureReference:9986811] Akt1 mediates neuronal differentiation in zebrafish via a reciprocal interaction with notch signaling [LiteratureReference:9986801] Hydrogen Sulfide Prevents Synaptic Plasticity from VD-Induced Damage via Akt/GSK-3β Pathway and Notch Signaling Pathway in Rats [LiteratureReference:9986816] Pten is necessary for the quiescence and maintenance of adult muscle stem cells |
| modified | [InstanceEdit:9986824] Orlic-Milacic, Marija, 2026-04-06 |
| text | Constitutively active AKT isoforms, AKT1, AKT2 and AKT3, were reported to downregulate transcription mediated by the NOTCH1 intracellular domain fagment NICD1 through AKT-mediated phosphorylation of cytosolic NICD1, which inhibits nuclear translocation of NICD1 and activation of target promoters (Song et al. 2008). In another study, AKT1 was shown to phosphorylate NOTCH4 intracellular domain fragment NICD4 on four serine residues which are not conserved in all four NOTCH isoforms, leading to binding of phosphorylated NICD4 to 14-3-3-zeta (YWHAZ) and its retention in the cytosol (Ramakrishnan et al. 2015). In mouse retinal progenitors, Akt activation inhibits Nicd1-mediated transcriptional activity, leading to reduced formation of Nicd1 transcription activation complexes with Rbpj (Jo et al. 2012). Pten, a negative regulator of Akt activation, is required to maintain Nicd1 transcriptional activity in mouse retinal progenitors (Jo et al. 2012). Pten is also needed to maintain Notch1 signaling in adult mouse skeletal stem cells in which Akt-mediated phosphorylation of Foxo1 impairs Foxo1-facilitated formation of Notch1 transcription activation complexes with Rbpj (Yue et al. 2017). In a model of vascular dementia-induced neuronal injury in rats, AKT was reported to downregulate NOTCH transcriptional activity by inactivating GSK3B (Liu et al. 2015). Inhibition of AKT leads to activating phosphorylation of NICD1 by GSK3B, which promotes nuclear transcloation and transcriptional activity of NICD1 (Liu et al. 2016). Contrary to these findings, AKT-mediated phosphorylation of NICD1 on a serine residue was reported to promote nuclear translocation and transcriptional activity of NICD1 in gastric cancer (Zhou et al. 2025). During neuronal development in zebrafish are part of a positive feedback loop that maintains neuronal precursors and prevents neuronal differentiation, with Akt activating Notch signaling, and Notch signaling increasing the expression level of Akt (Cheng et al. 2013). |
| (summation) | [Reaction:9986781] AKT phosphorylates NICD1 [Homo sapiens] |
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