Lysine is required for growth factor-induced mTORC1 activation

• Published in: Biochemical and biophysical research communications Vol. 533; no. 4; pp. 945 - 951
• Main Authors: Jang, Se-Kyeong, Hong, Sung-Eun, Lee, Da-Hee, Hong, Jungil, Park, In-Chul, Jin, Hyeon-Ok
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17.12.2020
• Subjects: A549 Cells; Amino acid; AMP-Activated protein kinase; AMP-Activated Protein Kinases - antagonists & inhibitors; AMP-Activated Protein Kinases - genetics; AMP-Activated Protein Kinases - metabolism; Carcinoma, Non-Small-Cell Lung - metabolism; Cell Line, Tumor; Culture Media, Serum-Free; Gene Knockdown Techniques; General control nonderepressible 2; Humans; Insulin - administration & dosage; Insulin-Like Growth Factor I - administration & dosage; Lung Neoplasms - metabolism; Lysine; Lysine - administration & dosage; Lysine - deficiency; Lysine - metabolism; Mechanistic target of rapamycin complex 1; Mechanistic Target of Rapamycin Complex 1 - metabolism; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; RNA, Small Interfering - genetics; General control nonderepressible 2; AMP-Activated protein kinase; Amino acid; Lysine; Mechanistic target of rapamycin complex 1
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2020.09.100

Mechanistic target of rapamycin complex 1 (mTORC1) integrates various environmental signals to regulate cell growth and metabolism. mTORC1 activity is sensitive to changes in amino acid levels. Here, we investigated the effect of lysine on mTORC1 activity in non-small cell lung cancer (NSCLC) cells. Lysine deprivation suppressed mTORC1 activity and lysine replenishment restored the decreased mTORC1 activity in lysine-deprived cells. Supplementing growth factors, such as insulin growth factor-1 or insulin restored the decreased mTORC1 activity in serum-deprived cells. However, in serum/lysine-deprived cells, supplementing growth factors was not sufficient to restore mTORC1 activity, suggesting that growth factors could not activate mTORC1 efficiently in the absence of lysine. General control nonderepressible 2 and AMP-activated protein kinase were involved in lysine deprivation-mediated inhibition of mTORC1. Taken together, these results suggest that lysine might play role in the regulation of mTORC1 activation in NSCLC cells. •Lysine deprivation inhibits mTORC1 activity.•Lysine replenishment restores the decreased mTORC1 activity by lysine deprivation.•Lysine is necessary for growth factor-induced mTORC1 activation.•GCN2 and AMPK are involved in lysine deprivation-mediated inhibition of mTORC1.