The regulatory mechanism of amino acids on milk protein and fat synthesis in mammary epithelial cells: a mini review

References

• Macias H, Hinck L. Mammary gland development. Wiley Interdiscip Rev Dev Biol. 2012;1(4):533–557.
   PubMed Web of Science ®Google Scholar
• Capuco AV, Choudhary RK. Symposium review: determinants of milk production: understanding population dynamics in the bovine mammary epithelium. J Dairy Sci. 2020;103(3):2928–2940.
   PubMed Web of Science ®Google Scholar
• Osorio JS, Lohakare J, Bionaz M. Biosynthesis of milk fat, protein, and lactose: roles of transcriptional and posttranscriptional regulation. Physiol Genomics. 2016;48(4):231–256.
   PubMed Web of Science ®Google Scholar
• Wang F, Shi H, Wang S, Wang Y, Cao Z, Li S. Amino acid metabolism in dairy cows and their regulation in milk synthesis. Curr Drug Metab. 2019;20(1):36–45.
   PubMed Web of Science ®Google Scholar
• Li N, Zhao F, Wei C, et al. Function of SREBP1 in the milk fat synthesis of dairy cow mammary epithelial cells. Int J Mol Sci. 2014;15(9):16998–17013.
   PubMed Web of Science ®Google Scholar
• Huang J, Guesthier MA, Burgos SA. AMP-activated protein kinase controls lipid and lactose synthesis in bovine mammary epithelial cells. J Dairy Sci. 2020;103(1):340–351.
   PubMed Web of Science ®Google Scholar
• Chen F, Chen B, Guan W, et al. Metabolic transition of milk lactose synthesis and up-regulation by AKT1 in sows from late pregnancy to lactation. Cell Biochem Biophys. 2017;75(1):131–138.
   PubMed Web of Science ®Google Scholar
• Villagrán M, Muñoz M, Inostroza E, et al. GLUT1 and GLUT8 support lactose synthesis in Golgi of murine mammary epithelial cells. J Physiol Biochem. 2019;75(2):209–215.
   PubMed Web of Science ®Google Scholar
• Efeyan A, Comb WC, Sabatini DM. Nutrient-sensing mechanisms and pathways. Nature. 2015;517(7534):302–310.
   PubMed Web of Science ®Google Scholar
• Liu GY, Sabatini DM. mTOR at the nexus of nutrition, growth, ageing and disease. Nat Rev Mol Cell Biol. 2020;21(4):183–203.
   PubMed Web of Science ®Google Scholar
• Saxton RA, Sabatini DM. mTOR signaling in Growth, Metabolism, and Disease. Cell. 2017;168(6):960–976.
   PubMed Web of Science ®Google Scholar
• Jiang Q, He L, Hou Y, et al. Alpha-ketoglutarate enhances milk protein synthesis by porcine mammary epithelial cells. Amino Acids. 2016;48(9):2179–2188.
   PubMed Web of Science ®Google Scholar
• Zhang MC, Zhao SG, Wang SS, et al. d-Glucose and amino acid deficiency inhibits casein synthesis through JAK2/STAT5 and AMPK/mTOR signaling pathways in mammary epithelial cells of dairy cows. J Dairy Sci. 2018;101(2):1737–1746.
   PubMed Web of Science ®Google Scholar
• Cheng J, Zhang Y, Ge Y, et al. Sodium butyrate promotes milk fat synthesis in bovine mammary epithelial cells via GPR41 and its downstream signalling pathways. Life Sci. 2020; 259:118375.
   PubMed Web of Science ®Google Scholar
• Zhao Y, Guo X, Yan S, Shi B, Sheng R. Acetate regulates milk fat synthesis through the mammalian target of rapamycin/eukaryotic initiation factor 4E signaling pathway in bovine mammary epithelial cells. J Dairy Sci. 2021;104(1):337–345.
   PubMed Web of Science ®Google Scholar
• Liao XD, Zhou CH, Zhang J, et al. Effect of all-trans retinoic acid on casein and fatty acid synthesis in MAC-T cells. Asian-Australas J Anim Sci. 2020;33(6):1012–1022.
   PubMed Web of Science ®Google Scholar
• Huang X, Zang Y, Zhang M, Yuan X, Li M, Gao X. Nuclear factor of κB1 is a key regulator for the transcriptional activation of milk synthesis in bovine mammary epithelial cells. DNA Cell Biol. 2017;36(4):295–302.
   PubMed Web of Science ®Google Scholar
• Yu Y, Zhen Z, Qi H, Yuan X, Gao X, Zhang M. U2AF65 enhances milk synthesis and growth of bovine mammary epithelial cells by positively regulating the mTOR-SREBP-1c signalling pathway. Cell Biochem Funct. 2019;37(2):93–101.
   PubMed Web of Science ®Google Scholar
• Pauloin A, Chanat E. Prolactin and epidermal growth factor stimulate adipophilin synthesis in HC11 mouse mammary epithelial cells via the PI3-kinase/Akt/mTOR pathway. Biochim Biophys Acta. 2012;1823(5):987–996.
   PubMed Web of Science ®Google Scholar
• Galbaugh T, Cerrito MG, Jose CC, Cutler ML. EGF-induced activation of Akt results in mTOR-dependent p70S6 kinase phosphorylation and inhibition of HC11 cell lactogenic differentiation. BMC Cell Biol. 2006; 7:34.
   PubMedGoogle Scholar
• Sobolewska A, Gajewska M, Zarzyńska J, Gajkowska B, Motyl T. IGF-I, EGF, and sex steroids regulate autophagy in bovine mammary epithelial cells via the mTOR pathway. Eur J Cell Biol. 2009;88(2):117–130.
   PubMed Web of Science ®Google Scholar
• Sun J, Liu J, Huang B, et al. Kisspeptin-10 induces beta-casein synthesis via GPR54 and its downstream signaling pathways in bovine mammary epithelial cells. Int J Mol Sci. 2017;18(12):2621.
   PubMed Web of Science ®Google Scholar
• Yu Y, Yuan X, Li P, Wang Y, Yu M, Gao X. Vaccarin promotes proliferation of and milk synthesis in bovine mammary epithelial cells through the Prl receptor-PI3K signaling pathway. Eur J Pharmacol. 2020; 880:173190.
   PubMed Web of Science ®Google Scholar
• Yu M, Qi H, Gao X. Daidzein promotes milk synthesis and proliferation of mammary epithelial cells via the estrogen receptor alpha-dependent NFkappaB1 activation. Anim Biotechnol. 2020;13:1–10. May
   Google Scholar
• Luo C, Qi H, Huang X, et al. GlyRS is a new mediator of amino acid-induced milk synthesis in bovine mammary epithelial cells. J Cell Physiol. 2019;234(3):2973–2983.
   PubMed Web of Science ®Google Scholar
• Luo C, Zhao S, Zhang M, et al. SESN2 negatively regulates cell proliferation and casein synthesis by inhibition the amino acid-mediated mTORC1 pathway in cow mammary epithelial cells. Sci Rep. 2018;8(1):3912.
   PubMedGoogle Scholar
• Eberlé D, Hegarty B, Bossard P, Ferré P, Foufelle F. SREBP transcription factors: master regulators of lipid homeostasis. Biochimie. 2004;86(11):839–848.
   PubMed Web of Science ®Google Scholar
• Dorotea D, Koya D, Ha H. Recent insights into SREBP as a direct mediator of kidney fibrosis via lipid-independent pathways. Front Pharmacol. 2020;11:265.
   PubMed Web of Science ®Google Scholar
• Li X, Li P, Wang L, Zhang M, Gao X. Lysine enhances the stimulation of fatty acids on milk fat synthesis via the GPRC6A-PI3K-FABP5 signaling in bovine mammary epithelial cells. J Agric Food Chem. 2019;67(25):7005–7015.
   PubMed Web of Science ®Google Scholar
• Li P, Yu M, Zhou C, et al. FABP5 is a critical regulator of methionine- and estrogen-induced SREBP-1c gene expression in bovine mammary epithelial cells. J Cell Physiol. 2018;234(1):537–549.
   PubMed Web of Science ®Google Scholar
• Peterson TR, Sengupta SS, Harris TE, et al. mTOR complex 1 regulates lipin 1 localization to control the SREBP pathway. Cell. 2011;146(3):408–420.
   PubMed Web of Science ®Google Scholar
• Dong Q, Majumdar G, O'Meally RN, Cole RN, Elam MB, Raghow R. Insulin-induced de novo lipid synthesis occurs mainly via mTOR-dependent regulation of proteostasis of SREBP-1c. Mol Cell Biochem. 2020;463(1–2):13–31.
   PubMed Web of Science ®Google Scholar
• Li P, Zhou C, Li X, Yu M, Li M, Gao X. CRTC2 is a key mediator of amino acid-induced milk fat synthesis in mammary epithelial cells. J Agric Food Chem. 2019;67(37):10513–10520.
   PubMed Web of Science ®Google Scholar
• Hu L, Chen Y, Cortes IM, et al. Supply of methionine and arginine alters phosphorylation of mechanistic target of rapamycin (mTOR), circadian clock proteins, and α-s1-casein abundance in bovine mammary epithelial cells. Food Funct. 2020;11(1):883–894.
   PubMed Web of Science ®Google Scholar
• Gao HN, Hu H, Zheng N, Wang JQ. Leucine and histidine independently regulate milk protein synthesis in bovine mammary epithelial cells via mTOR signaling pathway. J Zhejiang Univ Sci B. 2015;16(6):560–572.
   PubMed Web of Science ®Google Scholar
• Zhou MM, Wu YM, Liu HY, Liu JX. Effects of phenylalanine and threonine oligopeptides on milk protein synthesis in cultured bovine mammary epithelial cells. J Anim Physiol Anim Nutr. 2015;99(2):215–220.
   PubMed Web of Science ®Google Scholar
• Dong X, Zhou Z, Wang L, et al. Increasing the availability of threonine, isoleucine, valine, and leucine relative to lysine while maintaining an ideal ratio of lysine:methionine alters mammary cellular metabolites, mammalian target of rapamycin signaling, and gene transcription. J Dairy Sci. 2018;101(6):5502–5514.
   PubMed Web of Science ®Google Scholar
• Arriola Apelo SI, Singer LM, Lin XY, McGilliard ML, St-Pierre NR, Hanigan MD. Isoleucine, leucine, methionine, and threonine effects on mammalian target of rapamycin signaling in mammary tissue. J Dairy Sci. 2014;97(2):1047–1056.
   PubMed Web of Science ®Google Scholar
• Luo C, Yu M, Li S, Huang X, Qi H, Gao X. Methionine stimulates GlyRS phosphorylation via the GPR87-CDC42/Rac1-MAP3K10 signaling pathway. Biochem Biophys Res Commun. 2020;523(4):847–852.
   PubMed Web of Science ®Google Scholar
• Yu M, Wang Y, Wang Z, Liu Y, Yu Y, Gao X. Taurine promotes milk synthesis via the GPR87-PI3K-SETD1A signaling in BMECs. J Agric Food Chem. 2019;67(7):1927–1936.
   PubMed Web of Science ®Google Scholar
• Qi H, Meng C, Jin X, Li X, Li P, Gao X. Methionine promotes milk protein and fat synthesis and cell proliferation via the SNAT2-PI3K signaling pathway in bovine mammary epithelial cells. J Agric Food Chem. 2018;66(42):11027–11033.
   PubMed Web of Science ®Google Scholar
• Qiu Y, Qu B, Zhen Z, Yuan X, Zhang L, Zhang M. Leucine promotes milk synthesis in bovine mammary epithelial cells via the PI3K-DDX59 signaling. J Agric Food Chem. 2019;67(32):8884–8895.
   PubMed Web of Science ®Google Scholar
• Zhang J, He W, Yi D, et al. Regulation of protein synthesis in porcine mammary epithelial cells by L-valine. Amino Acids. 2019;51(4):717–726.
   PubMed Web of Science ®Google Scholar
• Gao HN, Zhao SG, Zheng N, et al. Combination of histidine lysine methionine and leucine promotes beta-casein synthesis via the mechanistic target of rapamycin signaling pathway in bovine mammary epithelial cells. J Dairy Sci. 2017;100(9):7696–7709.
   PubMed Web of Science ®Google Scholar
• Li S, Hosseini A, Danes M, Jacometo C, Liu J, Loor JJ. Essential amino acid ratios and mTOR affect lipogenic gene networks and miRNA expression in bovine mammary epithelial cells. J Anim Sci Biotechnol. 2016;7:44.
   PubMed Web of Science ®Google Scholar
• Wang F, van Baal J, Ma L, et al. Short communication: relationship between lysine/methionine ratios and glucose levels and their effects on casein synthesis via activation of the mechanistic target of rapamycin signaling pathway in bovine mammary epithelial cells. J Dairy Sci. 2019;102(9):8127–8133.
   PubMed Web of Science ®Google Scholar
• Dong X, Zhou Z, Saremi B, Helmbrecht A, Wang Z, Loor JJ. Varying the ratio of Lys:Met while maintaining the ratios of Thr:Phe, Lys:Thr, Lys:His, and Lys:Val alters mammary cellular metabolites, mammalian target of rapamycin signaling, and gene transcription. J Dairy Sci. 2018;101(2):1708–1718.
   PubMed Web of Science ®Google Scholar
• Zheng L, Zhang W, Zhou Y, Li F, Wei H, Peng J. Recent advances in understanding amino acid sensing mechanisms that regulate mTORC1. Int J Mol Sci. 2016;17(10):1636.
   PubMed Web of Science ®Google Scholar
• Wang J, Hua T, Liu ZJ. Structural features of activated GPCR signaling complexes. Curr Opin Struct Biol. 2020; 63:82–89.
   PubMed Web of Science ®Google Scholar
• Insel PA, Sriram K, Gorr MW, et al. GPCRomics: an approach to discover GPCR drug targets. Trends Pharmacol Sci. 2019;40(6):378–387.
   PubMed Web of Science ®Google Scholar
• Nelson G, Chandrashekar J, Hoon MA, et al. An amino-acid taste receptor. Nature. 2002;416(6877):199–202.
   PubMed Web of Science ®Google Scholar
• Wu SV, Rozengurt N, Yang M, Young SH, Sinnett-Smith J, Rozengurt E. Expression of bitter taste receptors of the T2R family in the gastrointestinal tract and enteroendocrine STC-1 cells. Proc Natl Acad Sci USA. 2002;99(4):2392–2397.
   PubMed Web of Science ®Google Scholar
• Wauson EM, Zaganjor E, Cobb MH. Amino acid regulation of autophagy through the GPCR TAS1R1-TAS1R3. Autophagy. 2013;9(3):418–419.
   PubMed Web of Science ®Google Scholar
• Wang Y, Liu J, Wu H, Fang X, Chen H, Zhang C. Amino acids regulate mTOR pathway and milk protein synthesis in a mouse mammary epithelial cell line is partly mediated by T1R1/T1R3. Eur J Nutr. 2017;56(8):2467–2474.
   PubMed Web of Science ®Google Scholar
• Zhou Y, Zhou Z, Peng J, Loor JJ. Methionine and valine activate the mammalian target of rapamycin complex 1 pathway through heterodimeric amino acid taste receptor (TAS1R1/TAS1R3) and intracellular Ca2+ in bovine mammary epithelial cells. J Dairy Sci. 2018;101(12):11354–11363.
   PubMed Web of Science ®Google Scholar
• Liu J, Wang Y, Li D, et al. Milk protein synthesis is regulated by T1R1/T1R3 a G protein-coupled taste receptor through the mTOR pathway in the mouse mammary gland. Mol Nutr Food Res. 2017;61(9):1601017.
   Web of Science ®Google Scholar
• Pi M, Nishimoto SK, Quarles LD. GPRC6A: Jack of all metabolism (or master of none). Mol Metab. 2017;6(2):185–193.
   PubMed Web of Science ®Google Scholar
• Jørgensen CV, Bräuner-Osborne H. Pharmacology and physiological function of the orphan GPRC6A receptor. Basic Clin Pharmacol Toxicol. 2020;126(Suppl 6):77–87.
   PubMedGoogle Scholar
• Wellendorph P, Hansen KB, Balsgaard A, Greenwood JR, Egebjerg J, Bräuner-Osborne H. Deorphanization of GPRC6A: a promiscuous L-alpha-amino acid receptor with preference for basic amino acids. Mol Pharmacol. 2005;67(3):589–597.
   PubMed Web of Science ®Google Scholar
• Ye R, Pi M, Nooh MM, Bahout SW, Quarles LD. Human GPRC6A mediates testosterone-induced mitogen-activated protein kinases and mTORC1 signaling in prostate cancer cells. Mol Pharmacol. 2019;95(5):563–572.
   PubMed Web of Science ®Google Scholar
• Fujiwara T, Kanazawa S, Ichibori R, et al. L-arginine stimulates fibroblast proliferation through the GPRC6A-ERK1/2 and PI3K/Akt pathway. PLoS One. 2014;9(3):e92168.
   PubMed Web of Science ®Google Scholar
• Yahyaoui R, Pérez-Frías J. Amino acid transport defects in human inherited metabolic disorders. Int J Mol Sci. 2019;21(1):119.
   PubMed Web of Science ®Google Scholar
• Bröer S. Amino acid transporters as targets for cancer therapy: why where when and how. Int J Mol Sci. 2020;21(17):6156.
   PubMed Web of Science ®Google Scholar
• Goberdhan DC, Wilson C, Harris AL. Amino acid sensing by mTORC1: intracellular transporters mark the spot. Cell Metab. 2016;23(4):580–589.
   PubMed Web of Science ®Google Scholar
• Wyant GA, Abu-Remaileh M, Wolfson RL, et al. mTORC1 activator SLC38A9 is required to efflux essential amino acids from lysosomes and use protein as a nutrient. Cell. 2017;171(3):642–654.e12.
   PubMed Web of Science ®Google Scholar
• Zoncu R, Bar-Peled L, Efeyan A, Wang S, Sancak Y, Sabatini DM. mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase. Science. 2011;334(6056):678–683.
   PubMed Web of Science ®Google Scholar
• Salisbury TB, Arthur S. The regulation and function of the L-type amino acid transporter 1 (LAT1) in cancer. Int J Mol Sci. 2018;19(8):2373.
   PubMed Web of Science ®Google Scholar
• Cao D, Mikosz AM, Ringsby AJ, et al. MicroRNA-126-3p inhibits angiogenic function of human lung microvascular endothelial cells via LAT1 (L-type amino acid transporter 1)-mediated mTOR (mammalian target of rapamycin) signaling. Arterioscler Thromb Vasc Biol. 2020;40(5):1195–1206.
   PubMed Web of Science ®Google Scholar
• Lin Y, Duan X, Lv H, et al. The effects of L-type amino acid transporter 1 on milk protein synthesis in mammary glands of dairy cows. J Dairy Sci. 2018;101(2):1687–1696.
   PubMed Web of Science ®Google Scholar
• Duan X, Lin Y, Lv H, Yang Y, Jiao H, Hou X. Methionine induces LAT1 expression in dairy cow mammary gland by activating the mTORC1 signaling pathway. DNA Cell Biol. 2017;36(12):1126–1133.
   PubMed Web of Science ®Google Scholar
• Zhou J, Jiang M, Shi Y, Song S, Hou X, Lin Y. Prolactin regulates LAT1 expression via STAT5 (signal transducer and activator of transcription 5) signaling in mammary epithelial cells of dairy cows. J Dairy Sci. 2020;103(7):6627–6634.
   PubMed Web of Science ®Google Scholar
• Dai W, Zhao F, Liu J, Liu H. ASCT2 is involved in SARS-mediated β-casein synthesis of bovine mammary epithelial cells with methionine supply. J Agric Food Chem. 2020;68(46):13038–13045.
   PubMed Web of Science ®Google Scholar
• Lin X, Li S, Zou Y, Zhao FQ, Liu J, Liu H. Lysine stimulates protein synthesis by promoting the expression of ATB0,+ and Activating the mTOR Pathway in Bovine Mammary Epithelial Cells. J Nutr. 2018;148(9):1426–1433.
   PubMed Web of Science ®Google Scholar
• Masson GR. Towards a model of GCN2 activation. Biochem Soc Trans. 2019;47(5):1481–1488.
   PubMedGoogle Scholar
• Edick AM, Audette J, Burgos SA. CRISPR-Cas9-mediated knockout of GCN2 reveals a critical role in sensing amino acid deprivation in bovine mammary epithelial cells. J Dairy Sci. 2021;104(1):1123–1135.
   PubMed Web of Science ®Google Scholar
• Ren W, Li Y, Xia X, et al. Arginine inhibits the malignant transformation induced by interferon-gamma through the NF-κB-GCN2/eIF2α signaling pathway in mammary epithelial cells in vitro and in vivo. Exp Cell Res. 2018;368(2):236–247.
   PubMed Web of Science ®Google Scholar
• Xia X, Che Y, Gao Y, et al. Arginine supplementation recovered the IFN-γ-mediated decrease in milk protein and fat synthesis by inhibiting the GCN2/eIF2α pathway, which induces autophagy in primary bovine mammary epithelial cells. Mol Cells. 2016;39(5):410–417.
   PubMed Web of Science ®Google Scholar
• Yakobov N, Debard S, Fischer F, Senger B, Becker HD. Cytosolic aminoacyl-tRNA synthetases: unanticipated relocations for unexpected functions. Biochim Biophys Acta Gene Regul Mech. 2018;1861(4):387–400.
   PubMed Web of Science ®Google Scholar
• Han JM, Jeong SJ, Park MC, et al. Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway. Cell. 2012;149(2):410–424.
   PubMed Web of Science ®Google Scholar
• Yoon MS, Son K, Arauz E, Han JM, Kim S, Chen J. Leucyl-tRNA synthetase activates Vps34 in amino acid-sensing mTORC1 signaling. Cell Rep. 2016;16(6):1510–1517.
   PubMed Web of Science ®Google Scholar
• Wang L, Lin Y, Bian Y, et al. Leucyl-tRNA synthetase regulates lactation and cell proliferation via mTOR signaling in dairy cow mammary epithelial cells. Int J Mol Sci. 2014;15(4):5952–5969.
   PubMed Web of Science ®Google Scholar
• Yu M, Luo C, Huang X, et al. Amino acids stimulate glycyl-tRNA synthetase nuclear localization for mammalian target of rapamycin expression in bovine mammary epithelial cells. J Cell Physiol. 2019;234(5):7608–7621.
   PubMed Web of Science ®Google Scholar
• Dai WT, White RR, Liu JX, Liu HY. Seryl-tRNA synthetase-mediated essential amino acids regulate β-casein synthesis via cell proliferation and mammalian target of rapamycin (mTOR) signaling pathway in bovine mammary epithelial cells. J Dairy Sci. 2018;101(11):10456–10468.
   PubMed Web of Science ®Google Scholar
• Dai W, Zhao F, Liu J, Liu H. Seryl-tRNA synthetase is involved in methionine stimulation of β-casein synthesis in bovine mammary epithelial cells. Br J Nutr. 2020;123(5):489–498.
   PubMed Web of Science ®Google Scholar
• Zhang M, Chen D, Zhen Z, Ao J, Yuan X, Gao X. Annexin A2 positively regulates milk synthesis and proliferation of bovine mammary epithelial cells through the mTOR signaling pathway. J Cell Physiol. 2018;233(3):2464–2475.
   PubMed Web of Science ®Google Scholar
• Chen D, Yuan X, Liu L, et al. Mitochondrial ATAD3A regulates milk biosynthesis and proliferation of mammary epithelial cells from dairy cow via the mTOR pathway. Cell Biol Int. 2018;42(5):533–542.
   PubMed Web of Science ®Google Scholar
• Luo C, Zhao S, Dai W, Zheng N, Wang J. Proteomic analyses reveal GNG12 regulates cell growth and casein synthesis by activating the Leu-mediated mTORC1 signaling pathway. Biochim Biophys Acta Proteins Proteom. 2018;1866(11):1092–1101.
   PubMed Web of Science ®Google Scholar
• Jiang N, Wang Y, Yu Z, et al. WISP3 (CCN6) regulates milk protein synthesis and cell growth through mTOR signaling in dairy cow mammary epithelial cells. DNA Cell Biol. 2015;34(8):524–533.
   PubMed Web of Science ®Google Scholar
• Li L, Liu L, Qu B, Li X, Gao X, Zhang M. Twinfilin 1 enhances milk bio-synthesis and proliferation of bovine mammary epithelial cells via the mTOR signaling pathway. Biochem Biophys Res Commun. 2017;492(3):289–294.
   PubMed Web of Science ®Google Scholar
• Liu Y, Wang X, Zhen Z, Yu Y, Qiu Y, Xiang W. GRP78 regulates milk biosynthesis and the proliferation of bovinemammaryepithelial cells through the mTOR signaling pathway. Cell Mol Biol Lett. 2019; 24:57.
   PubMed Web of Science ®Google Scholar
• Li B, Basang Z, Hu L, Liu L, Jiang N. Septin6 regulates cell growth and casein synthesis in dairy cow mammary epithelial cells via mTORC1 pathway. J Dairy Res. 2019;86(2):181–187.
   PubMed Web of Science ®Google Scholar
• Mu Y, Zheng D, Wang C, Yu W, Zhang X. RagD regulates amino acid mediated-casein synthesis and cell proliferation via mTOR signalling in cow mammary epithelial cells. J Dairy Res. 2018;85(2):204–211.
   PubMed Web of Science ®Google Scholar
• Khudhair N, Luo C, Khalid A, et al. 14-3-3γ affects mTOR pathway and regulates lactogenesis in dairy cow mammary epithelial cells. In Vitro Cell Dev Biol Anim. 2015;51(7):697–704.
   PubMed Web of Science ®Google Scholar
• Wolfson RL, Chantranupong L, Saxton RA, et al. Sestrin2 is a leucine sensor for the mTORC1 pathway. Science. 2016;351(6268):43–48.
   PubMed Web of Science ®Google Scholar
• Luo C, Zheng N, Zhao S, Wang J. Sestrin2 negatively regulates casein synthesis through the SH3BP4-mTORC1 pathway in response to AA depletion or supplementation in cow mammary epithelial cells. J Agric Food Chem. 2019;67(17):4849–4859.
   PubMed Web of Science ®Google Scholar
• Yuan X, Zhen Z, Zhang M, Yu Y, Gao X, Ao JX. Cyclase-associated protein 1 is a key negative regulator of milk synthesis and proliferation of bovine mammary epithelial cells. Cell Biochem Funct. 2019;37(3):185–192.
   PubMed Web of Science ®Google Scholar
• Zhang X, Zhao F, Si Y, et al. GSK3β regulates milk synthesis in and proliferation of dairy cow mammary epithelial cells via the mTOR/S6K1 signaling pathway. Molecules. 2014;19(7):9435–9452.
   PubMed Web of Science ®Google Scholar
• Ao J, Wei C, Si Y, et al. Tudor-SN regulates milk synthesis and proliferation of bovine mammary epithelial cells. Int J Mol Sci. 2015;16(12):29936–29947.
   PubMed Web of Science ®Google Scholar
• Yuan X, Zhang L, Cui Y, Yu Y, Gao X, Ao J. NCOA5 is a master regulator of amino acid-induced mTOR activation and β-casein synthesis in bovine mammary epithelial cells. Biochem Biophys Res Commun. 2020;529(3):569–574.
   PubMed Web of Science ®Google Scholar
• Huo N, Yu M, Li X, Zhou C, Jin X, Gao X. PURB is a positive regulator of amino acid-induced milk synthesis in bovine mammary epithelial cells. J Cell Physiol. 2019;234(5):6992–7003.
   PubMed Web of Science ®Google Scholar
• Zhen Z, Zhang M, Yuan X, et al. DEAD-box helicase 6 (DDX6) is a new negative regulator for milk synthesis and proliferation of bovine mammary epithelial cells. In Vitro Cell Dev Biol Anim. 2018;54(1):52–60.
   PubMed Web of Science ®Google Scholar
• Dai H, Coleman DN, Lopes MG, et al. Alterations in immune and antioxidant gene networks by gamma-d-glutamyl-meso-diaminopimelic acid in bovine mammary epithelial cells are attenuated by in vitro supply of methionine and arginine. J Dairy Sci. 2021;104(1):776–785.
   PubMed Web of Science ®Google Scholar
• Chantranupong L, Scaria SM, Saxton RA, et al. The CASTOR proteins are arginine sensors for the mTORC1 pathway. Cell. 2016;165(1):153–164.
   PubMed Web of Science ®Google Scholar
• Gu X, Orozco JM, Saxton RA, Condon KJ, Liu GY, Krawczyk PA, et al. SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway. Science. 2017;358(6364):813–818.
   PubMed Web of Science ®Google Scholar