Phosphorylation-Dependent Inhibition of Akt1

Balasuriya, Nileeka; McKenna, McShane; Liu, Xuguang; Li, Shawn S.‐C.; O’Donoghue, Patrick

doi:10.20944/preprints201807.0393.v1

Cited by 2 publications

(3 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MK‐801 also blocked the binding of Akt1‐PIAS1 (Figure S1B). The enzymatic activity of Akt1 is reported to be fully stimulated by both T308 and S473 phosphorylation 25,26 . We found that Bicuculline treatment increased Akt1 T308 phosphorylation, while relatively stable levels of S473 phosphorylation were maintained (Figure 1A).…”

Section: Resultsmentioning

confidence: 73%

“…The enzymatic activity of Akt1 is reported to be fully stimulated by both T308 and S473 phosphorylation. 25,26 We found that Bicuculline treatment increased Akt1 T308 phosphorylation, while relatively stable levels of S473 phosphorylation were maintained (Figure 1A). These data implicate that NMDA receptordependent neuronal activity upregulates Akt1 SUMO1ylation mainly by PIAS3 and facilitates Akt1 activity by accelerating T308 phosphorylation.…”

Section: Nmda Receptor-dependent Neuronal Activity Induces Akt1 Sumoylationmentioning

confidence: 89%

“…The brains isolated from Sprague-Dawley rats (postnatal days 21-30) of both sexes were incubated in ice-cold artificial cerebrospinal fluid (ACSF; 290-300 mOsm, pH 7. 26. Hippocampal slices (400μm) were prepared using a Vibroslicer from the middle of the hippocampus, incubated with ACSF saturated with 95% O 2 and 5% CO 2 at 28℃ for 1 hour, and ultimately subjected to electrophysiological recordings.…”

Section: Preparations For Hippocampal Slicesmentioning

confidence: 99%

See 2 more Smart Citations

Neuronal activity‐induced SUMOylation of Akt1 by PIAS3 is required for long‐term potentiation of synaptic transmission

et al. 2021

FASEB j.

View full text Add to dashboard Cite

Neuronal activity regulates spatial distribution of the SUMOylation system in cytosolic and dendritic sites, which has been implicated in learning, memory, and underlying synaptic structural and functional remodeling in the hippocampus. However, the functional target proteins for activated small ubiquitin-like modifiers (SUMOs) and downstream molecular consequences behind long-term potentiation (LTP) of synaptic plasticity remain to be elucidated. In this study, we showed that N-methyl-D-aspartate receptor-mediated neuronal activity induced the covalent modification of cytosolic Akt1 by small ubiquitin-like modifier 1 (SUMO1) in rat cortical and hippocampal CA1 neurons. Protein inhibitor of activated STAT3 (PIAS3) was involved in the activity-induced Akt1 SUMO1-ylation, and K64 and K276 residues were major SUMOylated sites. Importantly, Akt1 SUMOylation at K64 and K276 enhanced its enzymatic activity and facilitated T308 phosphorylation. Furthermore, the N-terminal SAP domain of PIAS3 bound Akt1 directly. The disruption of Akt1-PIAS3 interaction by Tat-SAP, a synthetic Tat-fused cell-permeable peptide containing PIAS3 SAP domain, inhibited neuronal activity-induced Akt1 SUMOylation and impaired LTP expression and late phase LTP maintenance in the hippocampus. Correlatedly, Tat-SAP not only blocked the LTP-related extracellular signalregulated kinase (ERK)1/2-Elk-1-brain-derived neurotrophic factor (BDNF)/Arc signaling, but also disrupted mammalian target of rapamycin (mTOR)-eIF4Ebinding protein 1 (4E-BP1) pathway. These findings reveal an activity-induced Akt1 SUMOylation by PIAS3 that contributes to ERK1/2-BDNF/Arc and mTOR-4E-BP1 cascades, and in turn, long-lasting excitatory synaptic responses.

show abstract

Section: Resultsmentioning

confidence: 73%

Section: Nmda Receptor-dependent Neuronal Activity Induces Akt1 Sumoylationmentioning

confidence: 89%

Section: Preparations For Hippocampal Slicesmentioning

confidence: 99%

See 1 more Smart Citation

Neuronal activity‐induced SUMOylation of Akt1 by PIAS3 is required for long‐term potentiation of synaptic transmission

et al. 2021

FASEB j.

View full text Add to dashboard Cite

show abstract

Delivery of Active AKT1 to Human Cells

Siddika

Balasuriya

Frederick

et al. 2022

Cells

Self Cite

View full text Add to dashboard Cite

Protein kinase B (AKT1) is a serine/threonine kinase and central transducer of cell survival pathways. Typical approaches to study AKT1 biology in cells rely on growth factor or insulin stimulation that activates AKT1 via phosphorylation at two key regulatory sites (Thr308, Ser473), yet cell stimulation also activates many other kinases. To produce cells with specific AKT1 activity, we developed a novel system to deliver active AKT1 to human cells. We recently established a method to produce AKT1 phospho-variants from Escherichia coli with programmed phosphorylation. Here, we fused AKT1 with an N-terminal cell penetrating peptide tag derived from the human immunodeficiency virus trans-activator of transcription (TAT) protein. The TAT-tag did not alter AKT1 kinase activity and was necessary and sufficient to rapidly deliver AKT1 protein variants that persisted in human cells for 24 h without the need to use transfection reagents. TAT-pAKT1T308 induced selective phosphorylation of the known AKT1 substrate GSK-3α, but not GSK-3β, and downstream stimulation of the AKT1 pathway as evidenced by phosphorylation of ribosomal protein S6 at Ser240/244. The data demonstrate efficient delivery of AKT1 with programmed phosphorylation to human cells, thus establishing a cell-based model system to investigate signaling that is dependent on AKT1 activity.

show abstract

Phosphorylation-Dependent Inhibition of Akt1

Cited by 2 publications

References 50 publications

Neuronal activity‐induced SUMOylation of Akt1 by PIAS3 is required for long‐term potentiation of synaptic transmission

Neuronal activity‐induced SUMOylation of Akt1 by PIAS3 is required for long‐term potentiation of synaptic transmission

Delivery of Active AKT1 to Human Cells

Contact Info

Product

Resources

About