Getting the Akt Together: Guiding Intracellular Akt Activity by PI3K

Yudushkin, Ivan

doi:10.3390/biom9020067

Cited by 57 publications

(38 citation statements)

References 84 publications

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“…Class I PI3Ks are composed of regulatory (p85α, p85β and p85γ) and catalytic (p110α, p110β, p110δ, and p110γ); among them, p110α and p110β are widely expressed in many tissues, while p110δ and p110γ are mainly expressed Fig. 1 Overview of the PI3K/AKT/mTOR signalling pathway in leukocytes [12,16]. Activation by ligands, including growth factors, results in the tyrosine phosphorylation of cell surface receptors.…”

Section: Pi3ksmentioning

confidence: 99%

“…Dysfunction of this pathway is related to not only the occurrence and development of tumours but also many other human diseases, such as leukaemia, diabetes, and schizophrenia [9][10][11]. Researchers have gradually gained a strong understanding of PI3K/AKT/mTOR signalling pathway regulation and function and agree that thoroughly elucidating the mechanism of PI3K/AKT/mTOR signal transmission and the related upstream and downstream molecules is necessary [12][13][14]. Such knowledge will help facilitate the use of this pathway as a target for treating tumours and other related diseases.…”

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confidence: 99%

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RETRACTED ARTICLE: Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours

et al. 2020

Cell Biosci

426

229

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The PI3 K/AKT/mTOR signalling pathway plays an important role in the regulation of signal transduction and biological processes such as cell proliferation, apoptosis, metabolism and angiogenesis. Compared with those of other signalling pathways, the components of the PI3K/AKT/mTOR signalling pathway are complicated. The regulatory mechanisms and biological functions of the PI3K/AKT/mTOR signalling pathway are important in many human diseases, including ischaemic brain injury, neurodegenerative diseases, and tumours. PI3K/AKT/mTOR signalling pathway inhibitors include single-component and dual inhibitors. Numerous PI3K inhibitors have exhibited good results in preclinical studies, and some have been clinically tested in haematologic malignancies and solid tumours. In this review, we briefly summarize the results of research on the PI3K/AKT/mTOR pathway and discuss the structural composition, activation, communication processes, regulatory mechanisms and biological functions of the PI3K/AKT/mTOR signalling pathway in the pathogenesis of neurodegenerative diseases and tumours.

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Section: Pi3ksmentioning

confidence: 99%

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confidence: 99%

RETRACTED ARTICLE: Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours

et al. 2020

Cell Biosci

426

229

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“…PI3K family kinases are important generators of lipid second messenger molecules that can recruit cytoplasmic proteins to the cellular membrane. Akt is a downstream target of PI3K activation, regulating anabolic processes via phosphorylating roughly 300 different substrates when it is activated in cells (41). PI3K/Akt signaling is essential for the regulation of inflammatory responses, at least in part via controlling intracellular NF-κB activity (42).…”

Section: Discussionmentioning

confidence: 99%

Cyclocarya paliurus ethanol leaf extracts protect against diabetic cardiomyopathy in db/db mice via regulating PI3K/Akt/NF-κB signaling

Wang

Zheng

et al. 2020

Food & Nutrition Research

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Background: Diabetic cardiomyopathy (DCM) is a serious complication of diabetes that can lead to significant mortality. Cyclocarya paliurus is a tree, the leaves of which are often utilized to prevent and treat diabetes mellitus. Whether C. paliurus leaves can prevent or treat DCM, however, it remains to be formally assessed. The present study was therefore designed to assess the ability of C. paliurus to protect against DCM in db/db mice. Methods: Male wild-type (WT) and db/db mice were administered C. paliurus ethanol leaf extracts (ECL) or appropriate vehicle controls daily via gavage, and levels of blood glucose in treated animals were assessed on a weekly basis. After a 10-week treatment, the levels of cardiac troponin I (cTn-I), lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), aspartate transaminase (AST), total triglycerides (TG), and total cholesterol (TC) in serum were measured. Activities of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) and the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 in heart tissues were detected. Hematoxylin-eosin (HE) and Masson staining were conducted. The protein expression that related with oxidative stress and inflammatory reaction was evaluated by Western blotting. Results: Compared with WT mice, the TG, TC, and blood glucose levels in db/db mice increased significantly, which were reduced by ECL treatment. Compared with WT mice, the levels of LDH, CK-MB, AST, and cTn-I in serum and MDA in heart tissues of db/db mice increased significantly. Activities of SOD, GSH-Px, and CAT in heart tissues of db/db mice decreased significantly. The levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) in heart tissues of db/db mice increased remarkably. However, ECL treatment improved the above pathological changes significantly. ECL alleviated pathological injury and fibrosis in heart tissues of mice. Western blotting showed that ECL increased Bcl-2 level and decreased Bax, cle-caspase-3, and clecaspase-9 expression. Furthermore, ECL inhibited NF-κB nuclear translocation and increased PI3K and p-Akt expressions. Popular scientific summary • Cyclocarya paliurus ethanol leaf extract (ECL) is able to protect against the development of diabetic cardiomyopathy in db/db mice. • The protective efficacy of ECL is associated with antioxidant, antiapoptotic, and anti-inflammatory mechanisms. • ECL is able to inhibit the activation and nuclear localization of NF-κB via promoting PI3K/Akt signaling in db/db mice.

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“…VacA activates Akt (also called protein kinase B) via PI3K (phosphatidylinositol 3-kinase) that phosphorylates GSK3β (glycogen synthase kinase 3β) [79]. Akt is phosphorylated and activated by two protein kinases called PDK1 (3-Phosphoinositide-dependent kinase 1) and mTORC2 (mammalian target of rapamycin complex 2) that also bind to PIP3 [80]. The GSK-3β regulates cell proliferation and survival, which is inhibited by Akt phosphorylation [81,82].…”

Section: Vacuolating Cytotoxin a And Gastric Cancermentioning

confidence: 99%

Molecular Mechanism of Helicobacter pylori-Induced Gastric Cancer

Alipour

2020

J Gastrointest Canc

126

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Introduction Various types of cancers threaten human life. The role of bacteria in causing cancer is controversial, but it has been determined that the Helicobacter pylori infection is one of the identified risk factors for gastric cancer. Helicobacter pylori infection is highly prevalent, and about half of the world , s population is infected with it. Objective The aim of this study was the role of Helicobacter pylori in the development of gastric cancer. Method We obtained information from previously published articles. Results and Conclusion The bacterium has various virulence factors, including cytotoxin-associated gene A, vacuolating cytotoxin A, and the different outer membrane proteins that cause cancer by different mechanisms. These virulence factors activate cell signaling pathways such as PI3-kinase/Akt, JAK/STAT and Ras, Raf, and ERK signaling that control cell proliferation. Uncontrolled proliferation can lead to cancer.

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Getting the Akt Together: Guiding Intracellular Akt Activity by PI3K

Cited by 57 publications

References 84 publications

RETRACTED ARTICLE: Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours

RETRACTED ARTICLE: Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours

Cyclocarya paliurus ethanol leaf extracts protect against diabetic cardiomyopathy in db/db mice via regulating PI3K/Akt/NF-κB signaling

Molecular Mechanism of Helicobacter pylori-Induced Gastric Cancer

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