scholarly journals Amino acid sensing and mTOR regulation: inside or out?

2009 ◽  
Vol 37 (1) ◽  
pp. 248-252 ◽  
Author(s):  
Deborah C.I. Goberdhan ◽  
Margret H. Ögmundsdóttir ◽  
Shubana Kazi ◽  
Bruno Reynolds ◽  
Shivanthy M. Visvalingam ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Growth Factor ◽  
Environmental Conditions ◽  
Detection System ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Amino Acid Sensing ◽  
The Impact ◽  
Mtor Signalling

mTOR (mammalian target of rapamycin) plays a key role in determining how growth factor, nutrient and oxygen levels modulate intracellular events critical for the viability and growth of the cell. This is reflected in the impact of aberrant mTOR signalling on a number of major human diseases and has helped to drive research to understand how TOR (target of rapamycin) is itself regulated. While it is clear that amino acids can affect TOR signalling, how these molecules are sensed by TOR remains controversial, perhaps because cells use different mechanisms as environmental conditions change. Even the question of whether they have an effect inside the cell or at its surface remains unresolved. The present review summarizes current ideas and suggests ways in which some of the models proposed might be unified to produce an amino acid detection system that can adapt to environmental change.

Amino acids and mTOR signalling in anabolic function

2007 ◽  
Vol 35 (5) ◽  
pp. 1187-1190 ◽  
Author(s):  
C.G. Proud
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Tuberous Sclerosis ◽  
Tuberous Sclerosis Complex ◽  
Ribosome Biogenesis ◽  
Mammalian Target Of Rapamycin ◽  
Single Amino Acid ◽  
Translational Machinery ◽  
Intracellular Amino Acids ◽  
Mtor Signalling

Amino acids regulate signalling through the mTORC1 (mammalian target of rapamycin, complex 1) and thereby control a number of components of the translational machinery, including initiation and elongation factors. mTORC1 also positively regulates other anabolic processes, in particular ribosome biogenesis. The most effective single amino acid is leucine. A key issue is how intracellular amino acids regulate mTORC1. This does not require the TSC1/2 (tuberous sclerosis complex 1/2) complex, which is involved in the activation of mTORC1, for example, by insulin. Progress in understanding the mechanisms responsible for this will be reviewed.

scholarly journals Post-exercise whey protein hydrolysate supplementation induces a greater increase in muscle protein synthesis than its constituent amino acid content

2013 ◽  
Vol 110 (6) ◽  
pp. 981-987 ◽  
Author(s):  
Atsushi Kanda ◽  
Kyosuke Nakayama ◽  
Tomoyuki Fukasawa ◽  
Jinichiro Koga ◽  
Minoru Kanegae ◽  
...  
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Whey Protein ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Acid Mixture ◽  
Post Exercise ◽  
The Impact ◽  
Mtor Signalling

It is well known that ingestion of a protein source is effective in stimulating muscle protein synthesis after exercise. In addition, there are numerous reports on the impact of leucine and leucine-rich whey protein on muscle protein synthesis and mammalian target of rapamycin (mTOR) signalling. However, there is only limited information on the effects of whey protein hydrolysates (WPH) on muscle protein synthesis and mTOR signalling. The aim of the present study was to compare the effects of WPH and amino acids on muscle protein synthesis and the initiation of translation in skeletal muscle during the post-exercise phase. Male Sprague–Dawley rats swam for 2 h to depress muscle protein synthesis. Immediately after exercise, the animals were administered either carbohydrate (CHO), CHO plus an amino acid mixture (AA) or CHO plus WPH. At 1 h after exercise, the supplements containing whey-based protein (AA and WPH) caused a significant increase in the fractional rate of protein synthesis (FSR) compared with CHO. WPH also caused a significant increase in FSR compared with AA. Post-exercise ingestion of WPH caused a significant increase in the phosphorylation of mTOR levels compared with AA or CHO. In addition, WPH caused greater phosphorylation of ribosomal protein S6 kinase and eukaryotic initiation factor 4E-binding protein 1 than AA and CHO. In contrast, there was no difference in plasma amino acid levels following supplementation with either AA or WPH. These results indicate that WPH may include active components that are superior to amino acids for stimulating muscle protein synthesis and initiating translation.

scholarly journals TREINAMENTO DE FORÇA/SOBRECARGA MECÂNICA E SINALIZAÇÃO DO COMPLEXO 1 DO ALVO DA RAPAMICINA EM MAMÍFEROS NA HIPERTROFIA MUSCULAR EM DIFERENTES MODELOS EXPERIMENTAIS: REVISÃO SISTEMÁTICA

2017 ◽  
Vol 25 (1) ◽  
pp. 168
Author(s):  
André Katayama Yamada ◽  
Vanessa Azevedo Voltarelli ◽  
Adriana Pertille ◽  
Carlos Roberto Bueno Júnior
Keyword(s):  
Skeletal Muscle ◽  
Amino Acid ◽  
Resistance Exercise ◽  
Strength Training ◽  
Muscle Hypertrophy ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Skeletal Muscle Hypertrophy ◽  
Mechanical Overload ◽  
Amino Acid Sensing

O objetivo deste artigo de revisão sistemática foi apresentar o envolvimento da sinalização de aminoácidos e mecanotransdução na ativação do complexo 1 do alvo da rapamicina em mamíferos (mTORC1) na musculatura esquelética de animais e a expressão e papel do mTORC1 em humanos submetidos ao treinamento de força/estímulo mecânico. Foi realizada uma busca na base de dados PubMed com as seguintes palavras-chave: mTORC1, mammalian target of rapamycin complex 1, resistance exercise, strength training, mechanical overload e skeletal muscle hypertrophy, amino acid sensing transporter e mechanotransduction. Evidências demonstram que a ativação do mTORC1 possui correlação positiva com a hipertrofia muscular induzida pelo treinamento de força/estímulo mecânico. O mTORC1 integra diversos sinais oriundos de aminoácidos (sinalização de transportadores e sensores) e estímulo mecânico/treinamento de força (mecanotransdução). Ademais, o emprego de modelos de camundongos mutantes, abordagens genéticas, farmacológicas, cultura de células, modelos experimentais de treinamento de força para animais, assim como estudos com humanos, vêm possibilitando a elucidação destes mecanismos moleculares.

scholarly journals A MAP4 kinase related to Ste20 is a nutrient-sensitive regulator of mTOR signalling

2007 ◽  
Vol 403 (1) ◽  
pp. 13-20 ◽  
Author(s):  
Greg M. Findlay ◽  
Lijun Yan ◽  
Julia Procter ◽  
Virginie Mieulet ◽  
Richard F. Lamb
Keyword(s):  
Amino Acids ◽  
Growth Factor ◽  
Cell Growth ◽  
Mammalian Target Of Rapamycin ◽  
Signalling Pathway ◽  
Initiation Factor ◽  
S6 Kinase ◽  
Eukaryotic Initiation Factor 4E ◽  
Mtor Signalling ◽  
Mtor Signalling Pathway

The mTOR (mammalian target of rapamycin) signalling pathway is a key regulator of cell growth and is controlled by growth factors and nutrients such as amino acids. Although signalling pathways from growth factor receptors to mTOR have been elucidated, the pathways mediating signalling by nutrients are poorly characterized. Through a screen for protein kinases active in the mTOR signalling pathway in Drosophila we have identified a Ste20 family member (MAP4K3) that is required for maximal S6K (S6 kinase)/4E-BP1 [eIF4E (eukaryotic initiation factor 4E)-binding protein 1] phosphorylation and regulates cell growth. Importantly, MAP4K3 activity is regulated by amino acids, but not the growth factor insulin and is not regulated by the mTORC1 inhibitor rapamycin. Our results therefore suggest a model whereby nutrients signal to mTORC1 via activation of MAP4K3.

scholarly journals Functional Amino Acids and Autophagy: Diverse Signal Transduction and Application

2021 ◽  
Vol 22 (21) ◽  
pp. 11427
Author(s):  
Chunchen Liu ◽  
Linbao Ji ◽  
Jinhua Hu ◽  
Ying Zhao ◽  
Lee J. Johnston ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Amino Acids ◽  
Amino Acid ◽  
Mammalian Target Of Rapamycin ◽  
Comprehensive Overview ◽  
Related Disease ◽  
Signal Relay ◽  
Amino Acid Levels ◽  
Amino Acid Sensing

Functional amino acids provide great potential for treating autophagy-related diseases by regulating autophagy. The purpose of the autophagy process is to remove unwanted cellular contents and to recycle nutrients, which is controlled by many factors. Disordered autophagy has been reported to be associated with various diseases, such as cancer, neurodegeneration, aging, and obesity. Autophagy cannot be directly controlled and dynamic amino acid levels are sufficient to regulate autophagy. To date, arginine, leucine, glutamine, and methionine are widely reported functional amino acids that regulate autophagy. As a signal relay station, mammalian target of rapamycin complex 1 (mTORC1) turns various amino acid signals into autophagy signaling pathways for functional amino acids. Deficiency or supplementation of functional amino acids can immediately regulate autophagy and is associated with autophagy-related disease. This review summarizes the mechanisms currently involved in autophagy and amino acid sensing, diverse signal transduction among functional amino acids and autophagy, and the therapeutic appeal of amino acids to autophagy-related diseases. We aim to provide a comprehensive overview of the mechanisms of amino acid regulation of autophagy and the role of functional amino acids in clinical autophagy-related diseases and to further convert these mechanisms into feasible therapeutic applications.

scholarly journals Transforming growth factor alpha: mutation of aspartic acid 47 and leucine 48 results in different biological activities.

1988 ◽  
Vol 8 (3) ◽  
pp. 1247-1252 ◽  
Author(s):  
E Lazar ◽  
S Watanabe ◽  
S Dalton ◽  
M B Sporn
Keyword(s):  
Amino Acids ◽  
Biological Activity ◽  
Amino Acid ◽  
Growth Factor ◽  
Aspartic Acid ◽  
Transforming Growth Factor ◽  
Biologically Active ◽  
Single Amino Acid ◽  
Transforming Growth Factor Alpha ◽  
Factor Alpha

To study the relationship between the primary structure of transforming growth factor alpha (TGF-alpha) and some of its functional properties (competition with epidermal growth factor (EGF) for binding to the EGF receptor and induction of anchorage-independent growth), we introduced single amino acid mutations into the sequence for the fully processed, 50-amino-acid human TGF-alpha. The wild-type and mutant proteins were expressed in a vector by using a yeast alpha mating pheromone promoter. Mutations of two amino acids that are conserved in the family of the EGF-like peptides and are located in the carboxy-terminal part of TGF-alpha resulted in different biological effects. When aspartic acid 47 was mutated to alanine or asparagine, biological activity was retained; in contrast, substitutions of this residue with serine or glutamic acid generated mutants with reduced binding and colony-forming capacities. When leucine 48 was mutated to alanine, a complete loss of binding and colony-forming abilities resulted; mutation of leucine 48 to isoleucine or methionine resulted in very low activities. Our data suggest that these two adjacent conserved amino acids in positions 47 and 48 play different roles in defining the structure and/or biological activity of TGF-alpha and that the carboxy terminus of TGF-alpha is involved in interactions with cellular TGF-alpha receptors. The side chain of leucine 48 appears to be crucial either indirectly in determining the biologically active conformation of TGF-alpha or directly in the molecular recognition of TGF-alpha by its receptor.

scholarly journals Activation of the SPS Amino Acid-Sensing Pathway in Saccharomyces cerevisiae Correlates with the Phosphorylation State of a Sensor Component, Ptr3

2007 ◽  
Vol 28 (2) ◽  
pp. 551-563 ◽  
Author(s):  
Zhengchang Liu ◽  
Janet Thornton ◽  
Mário Spírek ◽  
Ronald A. Butow
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Amino Acids ◽  
Amino Acid ◽  
Nuclear Translocation ◽  
Proteolytic Processing ◽  
Casein Kinase I ◽  
Positive Regulators ◽  
Amino Acid Permeases ◽  
Amino Acid Sensing ◽  
Amino Acid Sensor

ABSTRACT Cells of the budding yeast Saccharomyces cerevisiae sense extracellular amino acids and activate expression of amino acid permeases through the SPS-sensing pathway, which consists of Ssy1, an amino acid sensor on the plasma membrane, and two downstream factors, Ptr3 and Ssy5. Upon activation of SPS signaling, two transcription factors, Stp1 and Stp2, undergo Ssy5-dependent proteolytic processing that enables their nuclear translocation. Here we show that Ptr3 is a phosphoprotein whose hyperphosphorylation is increased by external amino acids and is dependent on Ssy1 but not on Ssy5. A deletion mutation in GRR1, encoding a component of the SCFGrr1 E3 ubiquitin ligase, blocks amino acid-induced hyperphosphorylation of Ptr3. We found that two casein kinase I (CKI) proteins, Yck1 and Yck2, previously identified as positive regulators of SPS signaling, are required for hyperphosphorylation of Ptr3. Loss- and gain-of-function mutations in PTR3 result in decreased and increased Ptr3 hyperphosporylation, respectively. We found that a defect in PP2A phosphatase activity leads to the hyperphosphorylation of Ptr3 and constitutive activation of SPS signaling. Two-hybrid analysis revealed interactions between the N-terminal signal transduction domain of Ssy1 with Ptr3 and Yck1. Our findings reveal that CKI and PP2A phosphatase play antagonistic roles in SPS sensing by regulating Ptr3 phosphorylation.

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