AKT serine/threonine kinase 1

Overview

AKT serine/threonine kinase 1 (Akt1) is a serine/threonine protein kinase and a central component of the phosphoinositide 3-kinase (PI3K)/AKT/mTOR signaling axis. It is widely involved in regulating cell survival, proliferation, metabolism, migration, and stress responses. In biomedical research, Akt1 is frequently treated as a key signaling node because changes in its phosphorylation state can reflect activation of upstream receptor pathways such as EGFR, MET, FLT1, and TGFBR-linked signaling, as well as downstream effects on targets including GSK3β, FOXO1, and mTOR.

Because of its broad role in oncogenic and metabolic signaling, Akt1 is a common target in studies of cancer progression, drug resistance, lipid metabolism, and tissue remodeling. It is also used as a pharmacological readout in studies evaluating pathway inhibition by agents such as berberine, sirolimus, ponatinib, deferasirox, nobiletin, and tea polyphenol extracts, as well as in mechanistic work on anti-PD-1 therapy, PD-1/PD-L1 regulation, and disease models involving liver cancer, melanoma, Parkinson's disease, venous malformations, and metabolic dysfunction–associated steatotic liver disease.

Focus of Latest Publications

Recent publications have used Akt1 primarily as a signaling target, pathway marker, or mechanistic node rather than as a standalone therapeutic agent. Across these studies, Akt1 was repeatedly linked to the PI3K/Akt signaling pathway and its downstream mTOR signaling, with phosphorylation of AKT serving as an indicator of pathway activation or suppression.

In a molecular design study using a Transformer-based framework with generative flow network (GFlowNet) methods and QSAR modeling, Akt1 was included alongside Dopamine receptor D2 and CXCR4 as a benchmark target for compound exploration. This indicates its continued use in computational drug discovery workflows, where target-aware molecular generation and scoring are applied to identify candidate ligands.

Several disease-focused studies examined Akt1 in the context of cancer biology. In venous malformations, activation of the PI3K/AKT/mTOR pathway was described as a pathogenic driver, and the study evaluated polymeric rapamycin nanoparticles encapsulating ponatinib as a strategy to induce regression in mice. In liver cancer-related work, TMEM45B was reported to promote MET signaling activation, with increased phosphorylation of downstream effectors AKT and ERK, supporting a role for Akt1 as part of MET-driven oncogenic signaling. Another liver cancer study linked FLT1-centered networks to Akt1, suggesting that Akt1 is embedded in broader endothelial and senescence-associated signaling circuits. In a separate hepatocellular context, cathepsin G was reported to promote hepatic lipid deposition by suppressing Akt, connecting AKT signaling to lipid metabolism and metabolic liver disease.

Akt1 was also implicated in therapeutic response and resistance. berberine enhanced cisplatin efficacy in ehrlich ascites carcinoma and was associated with downregulation of Akt1, Axl, Mertk, and Gas6 gene expression, suggesting that Akt1 suppression may contribute to improved antitumor effects and altered efferocytosis. In melanoma, deferasirox was used to disrupt iron-driven PI3K/AKT signaling and PD-L1 upregulation, linking Akt1 to immune evasion and iron metabolism. In lymphoma, AKT was highlighted as part of core survival networks together with B-cell receptor, JAK/STAT, and BCL2 apoptosis pathways, reinforcing its role in adaptive resistance and malignant cell survival.

Outside oncology, Akt1 appeared in studies of neuroprotection and cardioprotection. In Parkinson's disease research, DPP-4 inhibitors sitagliptin and vildagliptin were analyzed through network pharmacology and docking, with Akt1 emerging as a central node alongside DPP-4 and GSK3β, consistent with a role in autophagy modulation. In myocardial protection induced by vagal nerve stimulation preconditioning, myocardial phosphorylation of Akt and GSK-3β was evaluated, indicating AKT pathway involvement in early and delayed cardioprotective responses.

Akt1 was also used as a mechanistic readout in studies of natural products and pathway inhibitors. Nobiletin was reported to inhibit non-small cell lung cancer and synergize with an HDAC inhibitor by suppressing phosphorylation of the PI3K/AKT/mTOR pathway. Liupao tea polyphenol extract was found to prevent metabolic dysfunction–associated steatotic liver disease by downregulating the EGFR/pEGFR-AKT/pAKT-SREBP-1-ACC1 pathway through EGFR binding. In another study, elevated iron was described as activating PI3K/AKT signaling and upregulating PD-L1, providing a mechanistic rationale for iron chelation. These findings collectively position Akt1 as a convergence point for growth factor signaling, metabolic regulation, and immune modulation.