Lysine is required for growth factor-induced mTORC1 activation

Biochem Biophys Res Commun. 2020 Dec 17;533(4):945-951. doi: 10.1016/j.bbrc.2020.09.100. Epub 2020 Sep 30.

Abstract

Mechanistic target of rapamycincomplex 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 thatgrowth 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.

Keywords: AMP-Activated protein kinase; Amino acid; General control nonderepressible 2; Lysine; Mechanistic target of rapamycin complex 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • 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
  • Humans
  • Insulin / administration & dosage
  • Insulin-Like Growth Factor I / administration & dosage
  • Lung Neoplasms / metabolism*
  • Lysine / administration & dosage
  • Lysine / deficiency
  • Lysine / metabolism*
  • 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

Substances

  • Culture Media, Serum-Free
  • IGF1 protein, human
  • Insulin
  • RNA, Small Interfering
  • Insulin-Like Growth Factor I
  • EIF2AK4 protein, human
  • Mechanistic Target of Rapamycin Complex 1
  • Protein Serine-Threonine Kinases
  • AMP-Activated Protein Kinases
  • Lysine