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Literature summary for 6.1.1.4 extracted from

  • Sato, Y.; Sato, Y.; Suzuki, R.; Obeng, K.; Yoshizawa, F.
    Leucyl-tRNA synthetase is required for the myogenic differentiation of C2C12 myoblasts, but not for hypertrophy or metabolic alteration of myotubes (2018), Exp. Cell Res., 364, 184-190 .
    View publication on PubMed
Search for more literature for 6.1.1.4

Cloned(Commentary)

Cloned (Comment) Organism
gene Lars2, quantitative real-time PCR expression analysis Mus musculus

Protein Variants

Protein Variants Comment Organism
additional information siRNA-mediated knockdown of Lars decreases phosphorylated p70 S6 kinase and inhibits the differentiation of C2C12 mouse myoblasts into myotubes, as evidenced by a decreased fusion index and decreased mRNA and protein expression levels of myogenic markers. si-Lars decreases the level of insulin-like growth factor 2 (Igf2) mRNA expression from the early stages of differentiation, indicating the possibility of an association between the mTOR–IGF2 axis and Lars. But Lars knockdown does not decrease phosphorylated mTOR in differentiated myotubes, nor does it affect the hypertrophy of myotubes as evidenced by measuring their diameters and detecting the mRNA and protein expression of hypertrophy markers Mus musculus

Localization

Localization Comment Organism GeneOntology No. Textmining
mitochondrion
-
 Mus musculus 5739
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + L-leucine + tRNALeu Mus musculus
-
 AMP + diphosphate + L-leucyl-tRNALeu
-
 ?

Organism

Organism UniProt Comment Textmining
Mus musculus Q8VDC0
-
-

Source Tissue

Source Tissue Comment Organism Textmining
C2C12 cell
-
 Mus musculus
-
myoblast
-
 Mus musculus
-
myotube
-
 Mus musculus
-
skeletal muscle cell
-
 Mus musculus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + L-leucine + tRNALeu
-
 Mus musculus AMP + diphosphate + L-leucyl-tRNALeu
-
 ?

Synonyms

Synonyms Comment Organism
LARS
-
 Mus musculus
Leucyl-tRNA synthetase
-
 Mus musculus

Cofactor

Cofactor Comment Organism Structure
ATP
-
 Mus musculus

General Information

General Information Comment Organism
malfunction Lars knockdown does not decrease phosphorylated mTOR in differentiated myotubes, nor does it affect the hypertrophy of myotubes. Extracellular flux analysis shows that Lars knockdown does not affect the metabolism (glycolysis and mitochondrial respiration) of myotubes Mus musculus
physiological function leucyl-tRNA synthetase (Lars) is an intracellular sensor of leucine involved in the activation of mTOR signaling with a physiological role in skeletal muscle cells, potential roles of Lars for the activation of mTOR signaling, skeletal muscle cell differentiation, hypertrophy, and metabolism. Enzyme Lars directly binds to Rag GTPase, a known mediator of amino acid signaling to mTORC1, in a leucine-dependent manner and acts as a GTPase-activating protein for Rag GTPase to activate mTOR signaling. Lars is required for skeletal muscle differentiation through the activation of mTOR signaling, but not for hypertrophy or metabolic alteration of myotubes, link between Lars and mTOR activation in muscle cells and the physiological role of myoblast differentiation. Lars is essential for the activation of mTOR signaling in skeletal muscle cells and myogenic differentiation thought the induction of Igf2 expression Mus musculus