On the appropriateness of antibody selection to estimate mTORC1 activity

Figueiredo, Vandré Casagrande; Dungan, Cory M.; Peterson, Charlotte A.; McCarthy, John J.

doi:10.1111/apha.13354

Cited by 4 publications

(5 citation statements)

References 11 publications

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“…This activation is independent of an active EC‐coupling sequence, and mTORC1 signalling displays a dose‐response relationship with peak tension. To our knowledge no known residue within the mTORC1 reflects the direct kinase activity and therefore, we fully agree with Figueiredo et al to recommend that a meaningful snapshot of mTORC1 activation using western blotting should focus on mTORC1 first‐line downstream targets. However, in our setting no additional conclusion can be obtained from the presented supplementary experiments endorsing the primary conclusions of Rindom et al.…”

Section: Resultssupporting

confidence: 86%

“…As outlined in a review of Figueiredo et al and the current letter to editor, Figueiredo and co‐workers provide compelling rationalization that mTOR Ser 2448 phosphorylation as well as rpS6 Ser 235/236 phosphorylation reflect prior activation of p70S6K rather than mTORC1 activation as such. Figueiredo et al, while appreciating our experimental approach, argue that other phosphorylation sites indicative of mTORC1 activation is necessary to provide sufficient accuracy on interpretation of mTORC1 signalling. Specifically measurement of phosphorylation of p70S6K Thr 389 and 4E‐BP1 Thr 37/46 is proposed.…”

mentioning

confidence: 87%

“…Teasing out the sequence of phosphorylation of p‐p70S6K Thr 389 vs p‐mTOR Ser 2448 would require very comprehensive time course experiments, which is not within the immediate reach of the current response to the comment letter of Figueiredo et al However, we agree that a more elaborate time course would be highly relevant to implement in future similar studies. On the other hand, although convincing rationalization admittedly exist for the role of p70S6K, more knowledge could deservedly also be retrieved from gain‐of‐function/loss‐of‐function animal models.…”

mentioning

confidence: 91%

“…In a letter to the editor by Figueiredo et al, entitled ‘On the appropriateness of antibody selection to estimate mTORC1 activity’, the authors question our choice of mTORC1 biomarkers . We much appreciate the input and the possibility to emphasize our conclusions.…”

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confidence: 99%

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Estimation of p70S6K Thr³⁸⁹ and 4E‐BP1 Thr^37/46 phosphorylation support dependency of tension per se in a dose‐response relationship for downstream mTORC1 signalling

et al. 2019

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Section: Resultssupporting

confidence: 86%

mentioning

confidence: 87%

mentioning

confidence: 91%

mentioning

confidence: 99%

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Estimation of p70S6K Thr³⁸⁹ and 4E‐BP1 Thr^37/46 phosphorylation support dependency of tension per se in a dose‐response relationship for downstream mTORC1 signalling

et al. 2019

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“…In addition, mTORC1 is also a target of its downstream p70S6K, so mTOR Ser2448 phosphorylation may be the parallel change in mTORC1 activity under certain circumstances. Furthermore, the latest studies have shown that p70S6K Thr389 is considered a direct and reliable target to estimate mTORC1 activity (Figueiredo et al, 2020). Therefore, it is highly necessary to conduct experimental validation for this parameter in future studies.…”

mentioning

confidence: 99%

Exercise-Induced Autophagy Suppresses Sarcopenia Through Akt/mTOR and Akt/FoxO3a Signal Pathways and AMPK-Mediated Mitochondrial Quality Control

Zeng

Liang

et al. 2020

Front. Physiol.

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Exercise training is one of the most effective interventional strategies for sarcopenia in aged people. Nevertheless, the underlying mechanisms are not well recognized. Increasing studies have reported abnormal regulation of autophagy in aged skeletal muscle. Our current study aims to explore the efficiency of exercise interventions, including treadmill exercise, resistance exercise, alternating exercise with treadmill running and resistance exercise, and voluntary wheel running, on 21-month-old rats with sarcopenia and to detect the underlying mechanisms. Results showed the declined mass of gastrocnemius muscle with deficient autophagy and excessive apoptosis as a result of up-regulated Atrogin-1 and MuRF1, declined Beclin1 level and LC3-II/LC3-I ratio, accumulated p62, increased Bax, and reduced Bcl-2 levels, and also exhibited a defective mitochondrial quality control due to declined PGC-1α, Mfn2, Drp1, and PINK1 levels. However, 12-week exercise interventions suppressed the decline in mass loss of skeletal muscle, accompanied by down-regulated Atrogin-1 and MuRF1, increased Beclin1 level, improved LC3-II/LC3-I ratio, declined p62 level, and reduced Bax and increased Bcl-2 level, as well as enhanced mitochondrial function due to the increased PGC-1α, Mfn2, Drp1, and PINK1 levels. Moreover, exercise interventions also down-regulated the phosphorylation of Akt, mTOR, and FoxO3a, and up-regulated phosphorylated AMPK to regulate the functional status of autophagy and mitochondrial quality control. Therefore, exercise-induced autophagy is beneficial for remedying sarcopenia by modulating Akt/mTOR and Akt/FoxO3a signal pathways and AMPK-mediated mitochondrial quality control, and resistance exercise exhibits the best interventional efficiency.

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Mycoprotein ingestion stimulates protein synthesis rates to a greater extent than milk protein in rested and exercised skeletal muscle of healthy young men: a randomized controlled trial

Monteyne

Coelho

Porter

et al. 2020

The American Journal of Clinical Nutrition

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Background Mycoprotein is a fungal-derived sustainable protein-rich food source, and its ingestion results in systemic amino acid and leucine concentrations similar to that following milk protein ingestion. Objective We assessed the mixed skeletal muscle protein synthetic response to the ingestion of a single bolus of mycoprotein compared with a leucine-matched bolus of milk protein, in rested and exercised muscle of resistance-trained young men. Methods Twenty resistance-trained healthy young males (age: 22 ± 1 y, body mass: 82 ± 2 kg, BMI: 25 ± 1 kg·m−2) took part in a randomized, double-blind, parallel-group study. Participants received primed, continuous infusions of L-[ring-2H5]phenylalanine and ingested either 31 g (26.2 g protein: 2.5 g leucine) milk protein (MILK) or 70 g (31.5 g protein: 2.5 g leucine) mycoprotein (MYCO) following a bout of unilateral resistance-type exercise (contralateral leg acting as resting control). Blood and m. vastus lateralis muscle samples were collected before exercise and protein ingestion, and following a 4-h postprandial period to assess mixed muscle fractional protein synthetic rates (FSRs) and myocellular signaling in response to the protein beverages in resting and exercised muscle. Results Mixed muscle FSRs increased following MILK ingestion (from 0.036 ± 0.008 to 0.052 ± 0.006%·h−1 in rested, and 0.035 ± 0.008 to 0.056 ± 0.005%·h−1 in exercised muscle; P <0.01) but to a greater extent following MYCO ingestion (from 0.025 ± 0.006 to 0.057 ± 0.004%·h−1 in rested, and 0.024 ± 0.007 to 0.072 ± 0.005%·h−1 in exercised muscle; P <0.0001) (treatment × time interaction effect; P <0.05). Postprandial FSRs trended to be greater in MYCO compared with MILK (0.065 ± 0.004 compared with 0.054 ± 0.004%·h−1, respectively; P = 0.093) and the postprandial rise in FSRs was greater in MYCO compared with MILK (Delta 0.040 ± 0.006 compared with Delta 0.018 ± 0.005%·h−1, respectively; P <0.01). Conclusions The ingestion of a single bolus of mycoprotein stimulates resting and postexercise muscle protein synthesis rates, and to a greater extent than a leucine-matched bolus of milk protein, in resistance-trained young men. This trial was registered at clinicaltrials.gov as 660065600.

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On the appropriateness of antibody selection to estimate mTORC1 activity

Cited by 4 publications

References 11 publications

Estimation of p70S6K Thr³⁸⁹ and 4E‐BP1 Thr^37/46 phosphorylation support dependency of tension per se in a dose‐response relationship for downstream mTORC1 signalling

Estimation of p70S6K Thr³⁸⁹ and 4E‐BP1 Thr^37/46 phosphorylation support dependency of tension per se in a dose‐response relationship for downstream mTORC1 signalling

Exercise-Induced Autophagy Suppresses Sarcopenia Through Akt/mTOR and Akt/FoxO3a Signal Pathways and AMPK-Mediated Mitochondrial Quality Control

Mycoprotein ingestion stimulates protein synthesis rates to a greater extent than milk protein in rested and exercised skeletal muscle of healthy young men: a randomized controlled trial

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On the appropriateness of antibody selection to estimate mTORC1 activity

Cited by 4 publications

References 11 publications

Estimation of p70S6K Thr389 and 4E‐BP1 Thr37/46 phosphorylation support dependency of tension per se in a dose‐response relationship for downstream mTORC1 signalling

Estimation of p70S6K Thr389 and 4E‐BP1 Thr37/46 phosphorylation support dependency of tension per se in a dose‐response relationship for downstream mTORC1 signalling

Exercise-Induced Autophagy Suppresses Sarcopenia Through Akt/mTOR and Akt/FoxO3a Signal Pathways and AMPK-Mediated Mitochondrial Quality Control

Mycoprotein ingestion stimulates protein synthesis rates to a greater extent than milk protein in rested and exercised skeletal muscle of healthy young men: a randomized controlled trial

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Estimation of p70S6K Thr³⁸⁹ and 4E‐BP1 Thr^37/46 phosphorylation support dependency of tension per se in a dose‐response relationship for downstream mTORC1 signalling

Estimation of p70S6K Thr³⁸⁹ and 4E‐BP1 Thr^37/46 phosphorylation support dependency of tension per se in a dose‐response relationship for downstream mTORC1 signalling