Premium
Amino acids stimulate glycyl‐tRNA synthetase nuclear localization for mammalian target of rapamycin expression in bovine mammary epithelial cells
Author(s) -
Yu Mengmeng,
Luo Chaochao,
Huang Xin,
Chen Dongying,
Li Shanshan,
Qi Hao,
Gao Xuejun
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27523
Subject(s) - pi3k/akt/mtor pathway , amino acid , nuclear export signal , microbiology and biotechnology , phosphorylation , nuclear localization sequence , biology , mechanistic target of rapamycin , nuclear transport , p70 s6 kinase 1 , autophagy , biochemistry , cell nucleus , cytoplasm , signal transduction , apoptosis
Abstract Amino acids are required for the activation of mammalian target of rapamycin (mTOR) to increase cell growth, protein and lipid synthesis, and inhibit autophagy. However, the mechanism through which amino acids activate the mTOR signaling is still largely unknown. In our previous study, we discovered that glycyl‐tRNA synthetase (GlyRS) is a key mediator of amino‐acid‐induced mTOR expression and activation in bovine mammary epithelial cells (BMECs). Here we show that amino acids stimulate GlyRS nuclear localization for mTOR expression in BMECs. Met stimulates GlyRS nuclear localization, and the nuclear GlyRS is cleaved into a C‐terminus‐containing truncated form. We prove that GlyRS has a bipartite nuclear leading sequences, and GlyRS is phosphorylated at Thr544 and Ser704 in the cytoplasm under the stimulation of amino acids (Met, Leu, and Lys). The nuclear GlyRS physically binds to nuclear factor kappa B1, triggers its phosphorylation, thereby enhancing mRNA expression of its target genes including mTOR, S6K1, and 4EBP1. We further demonstrate that GlyRS is required for the inhibition of autophagy by Met. Thus our work elucidates that amino acids trigger GlyRS phosphorylation and nuclear localization to enhance the mRNA expression of mTOR.