Protein Phosphorylation as a Key Mechanism of mTORC1/2 Signaling Pathways

Tchevkina, Elena M.; Komelkov, A. V.

doi:10.5772/48274

Cited by 18 publications

(18 citation statements)

References 235 publications

(326 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…U-2 OS cells treated with leucettine L41, rapamycin or DMSO were analyzed for mTOR activation. mTOR phosphorylates 4E-BP1 at Thr70 (see Tchevkina and Komelkov, 2012, for review). 4E-BP1 phosphorylation was inhibited by rapamycin, as shown by the complete phospho-Thr70 signal disappearance (Fig.…”

Section: Resultsmentioning

confidence: 99%

cdc-Like/Dual-Specificity Tyrosine Phosphorylation–Regulated Kinases Inhibitor Leucettine L41 Induces mTOR-Dependent Autophagy: Implication for Alzheimer’s Disease

et al. 2013

View full text Add to dashboard Cite

Leucettines, a family of pharmacological inhibitors of dualspecificity tyrosine phosphorylation regulated kinases and cdclike kinases (CLKs), are currently under investigation for their potential therapeutic application to Down syndrome and Alzheimer's disease. We here report that leucettine L41 triggers bona fide autophagy in osteosarcoma U-2 OS cells and immortalized mouse hippocampal HT22 cells, characterized by microtubuleassociated protein light chain 3 membrane translocation and foci formation. Leucettine L41-triggered autophagy requires the Unc-51-like kinase and is sensitive to the phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin and 3-methyladenine, suggesting that it acts through the mammalian target of rapamycin (mTOR)/PI3K-dependent pathway. Leucettine L41 does not act by modifying the autophagic flux of vesicles. Leucettine L41-induced autophagy correlates best with inhibition of CLKs. Leucettine L41 modestly inhibited phosphatidylinositol-3-phosphate 5-kinase, FYVE domain-containing activity as tested both in vitro and in vivo, which may also contribute to autophagy induction. Altogether these results demonstrate that leucettines can activate the autophagic mTOR/PI3K pathway, a characteristic that may turn advantageous in the context of Alzheimer's disease treatment.

show abstract

Section: Resultsmentioning

confidence: 99%

cdc-Like/Dual-Specificity Tyrosine Phosphorylation–Regulated Kinases Inhibitor Leucettine L41 Induces mTOR-Dependent Autophagy: Implication for Alzheimer’s Disease

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Pre-treatment with 25 mM or 50 mM carnosine before inducing the oxidative stress attenuated the p38 phosphorylation when compared with the 0 mM carnosine + H 2 O 2 treatment (Fig 6A and 6C; P<0.05). However, the carnosine pre-treatment did not prevent the activation of p44/42 MAPK (Fig 6D and 6F; P>0.1) and SAPK/JNK The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that senses different cellular and extracellular signals to control proliferation, growth and survival [55]. Growth factors signaling lead to the activation of mTOR, which will in turn phosphorylates P70S6K and 4E-BP1, two downstream substrates known to regulate protein translation initiation and progression [56], whereas energy or nutrient depletion and stress signals suppress mTOR signaling.…”

Section: Plos Onementioning

confidence: 99%

Characterisation of intracellular molecular mechanisms modulated by carnosine in porcine myoblasts under basal and oxidative stress conditions

et al. 2020

View full text Add to dashboard Cite

Carnosine is a naturally occurring histidine-containing dipeptide present at high concentration in mammalian skeletal muscles. Carnosine was shown to affect muscle contraction, prevent the accumulation of oxidative metabolism by-products and act as an intracellular proton buffer maintaining the muscle acid-base balance. The present study was undertaken to gain additional knowledge about the intracellular mechanisms activated by carnosine in porcine myoblast cells under basal and oxidative stress conditions. Satellite cells were isolated from the skeletal muscles of 3 to 4 day-old piglets to study the effect of 0, 10, 25 and 50 mM carnosine pre-treatments in cells that were exposed (0.3 mM H 2 O 2) or not to an H 2 O 2-induced oxidative stress. Study results demonstrated that carnosine acts differently in myoblasts under oxidative stress and in basal conditions, the only exception being with the reduction of reactive oxygen species and protein carbonyls observed in both experimental conditions with carnosine pre-treatment. In oxidative stress conditions, carnosine pre-treatment increased the mRNA abundance of the nuclear factor, erythroid 2 like 2 (NEF2L2) transcription factor and several of its downstream genes known to reduce H 2 O 2. Carnosine prevented the H 2 O 2-mediated activation of p38 MAPK in oxidative stress conditions, whereas it triggered the activation of mTOR under basal conditions. Current results support the protective effect of carnosine against oxidative damage in porcine myoblast cells, an effect that would be mediated through the p38 MAPK intracellular signaling pathway. The activation of the mTOR signaling pathway under basal condition also suggest a role for carnosine in myoblasts proliferation, growth and survival.

show abstract

“…mTOR acts within two distinct multi‐protein complexes, mTORC1 and mTORC2, responsible for different physiological functions. While mTORC1 is involved mainly in the regulation of the translation initiation machinery influencing cell growth, proliferation and survival, mTORC2 participates in actin cytoskeleton rearrangements and cell survival . Rapamycin exerts its effect on memory differentiation by acting directly on mTORC1 in antigen‐specific CD8 + T cells .…”

Section: Discussionmentioning

confidence: 99%

Respiratory syncytial virus induces phosphorylation of mTOR at ser2448 in CD8 T cells from nasal washes of infected infants

Souza

Freitas

Fernandes

et al. 2015

Clinical and Experimental Immunology

View full text Add to dashboard Cite

Summary Respiratory syncytial virus (RSV)-specific CD81 T cell responses do not protect against reinfection. Activation of mammalian target of rapamycin (mTOR) impairs memory CD8 1 T cell differentiation. Our hypothesis was that RSV inhibits the formation of CD8 1 T cells memory responses through mTOR activation. To explore this, human and mouse T cells were used. RSV induced mTOR phosphorylation at Ser2448 in CD8 T cells. mTOR activation by RSV was completely inhibited using rapamycin. RSV-infected children presented higher mTOR gene expression on nasal washes comparing to children infected with metapneumovirus and rhinovirus. In addition, RSV-infected infants presented a higher frequency of CD8 1 pmTORser2448 1 T cells in nasal washes compared to RSV-negative infants.Rapamycin treatment increased the frequency of mouse CD8 RSV-M 282-90 pentamer-positive T cells and the frequency of RSV-specific memory T cells precursors. These data demonstrate that RSV is activating mTOR directly in CD8 T cells, indicating a role for mTOR during the course of RSV infection.

show abstract

Protein Phosphorylation as a Key Mechanism of mTORC1/2 Signaling Pathways

Cited by 18 publications

References 235 publications

cdc-Like/Dual-Specificity Tyrosine Phosphorylation–Regulated Kinases Inhibitor Leucettine L41 Induces mTOR-Dependent Autophagy: Implication for Alzheimer’s Disease

cdc-Like/Dual-Specificity Tyrosine Phosphorylation–Regulated Kinases Inhibitor Leucettine L41 Induces mTOR-Dependent Autophagy: Implication for Alzheimer’s Disease

Characterisation of intracellular molecular mechanisms modulated by carnosine in porcine myoblasts under basal and oxidative stress conditions

Respiratory syncytial virus induces phosphorylation of mTOR at ser2448 in CD8 T cells from nasal washes of infected infants

Contact Info

Product

Resources

About