Leucine induced dephosphorylation of Sestrin2 promotes mTORC1 activation

Cellular Signalling

Volumn 28, Issue 8, 2016, Pages 896-906

  Kimball, Scot R ^a   Gordon, Bradley S ^a,b   Moyer, Jenna E ^a   Dennis, Michael D ^a   Jefferson, Leonard S ^a  

^a PENN STATE COLLEGE OF MEDICINE   (United States)

^b UNIVERSITY OF CENTRAL FLORIDA   (United States)

Author keywords

Amino acids; Mechanistic target of rapamycin; Rag GTPases; Signaling; ULK1

Indexed keywords

GATOR2 PROTEIN; GUANOSINE TRIPHOSPHATASE; LEUCINE; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; PHOSPHOPROTEIN; PROTEIN KINASE; PROTEIN KINASE ULK1; RAPAMYCIN; SESTRIN2 PROTEIN; UNCLASSIFIED DRUG; MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1; MULTIPROTEIN COMPLEX; NUCLEAR PROTEIN; PROTEIN BINDING; SERINE THREONINE PROTEIN KINASE ULK1; SESN2 PROTEIN, HUMAN; TARGET OF RAPAMYCIN KINASE; ULK1 PROTEIN, MOUSE;

ANIMAL CELL; ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; ELECTROPHORETIC MOBILITY; HUMAN; HUMAN CELL; MASS SPECTROMETRY; MOUSE; MUTATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEPHOSPHORYLATION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; AMINO ACID SEQUENCE; ANIMAL; BIOLOGICAL MODEL; CHEMISTRY; DRUG EFFECTS; ELECTROPHORESIS; HEK293 CELL LINE; HELA CELL LINE; METABOLISM; PHOSPHORYLATION; SIGNAL TRANSDUCTION; SITE DIRECTED MUTAGENESIS; TIME FACTOR;

AMINO ACID SEQUENCE; ANIMALS; AUTOPHAGY-RELATED PROTEIN-1 HOMOLOG; ELECTROPHORESIS; HEK293 CELLS; HELA CELLS; HUMANS; LEUCINE; MASS SPECTROMETRY; MICE; MODELS, BIOLOGICAL; MULTIPROTEIN COMPLEXES; MUTAGENESIS, SITE-DIRECTED; NUCLEAR PROTEINS; PHOSPHORYLATION; PROTEIN BINDING; SIGNAL TRANSDUCTION; TIME FACTORS; TOR SERINE-THREONINE KINASES;

EID: 84966393355     PISSN: 08986568     EISSN: 18733913     Source Type: Journal    
DOI: 10.1016/j.cellsig.2016.03.008     Document Type: Article

References (34)

1. Buse M.G., Reid S.S. Leucine, a possible regulator of protein turnover in muscle. J. Clin. Invest. 1975, 56:1250-1261.
2. Fulks R.M., Li J.B., Goldberg A.L. Effects of insulin, glucose, and amino acids on protein turnover in rat diaphragm. J. Biol. Chem. 1975, 250:290-298.
3. Li J.B., Jefferson L.S. Influence of amino acid availability on protein turnover in perfused skeletal muscle. Biochim. Biophys. Acta 1978, 544:351-359.
4. Morgan H.E., Earl D.C., Broadus A., Wolpert E.B., Giger K.E., Jefferson L.S. Regulation of protein synthesis in heart muscle. I. Effect of amino acid levels on protein synthesis. J. Biol. Chem. 1971, 246:2152-2162.
5. Anthony J.C., Yoshizawa F., Anthony T.G., Vary T.C., Jefferson L.S., Kimball S.R. Leucine stimulates translation initiation in skeletal muscle of post-absorptive rats via a rapamycin-sensitive pathway. J. Nutr. 2000, 130:2413-2419.
6. Chantranupong L., Wolfson R.L., Orozco J.M., Saxton R.A., Scaria S.M., Bar-Peled L., Spooner E., Isasa M., Gygi S.P., Sabatini D.M. The sestrins interact with GATOR2 to negatively regulate the amino-acid-sensing pathway upstream of mTORC1. Cell Rep. 2014, 9:1-8.
7. Parmigiani A., Nourbakhsh A., Ding B., Wang W., Kim Y.C., Akopiants K., Guan K.L., Karin M., Budanov A.V. Sestrins inhibit mTORC1 kinase activation through the GATOR complex. Cell Rep. 2014, 9:1281-1291.
8. Jewell J.L., Kim Y.C., Russell R.C., Yu F.X., Park H.W., Plouffe S.W., Tagliabracci V.S., Guan K.L. Metabolism. Differential regulation of mTORC1 by leucine and glutamine. Science 2015, 347:194-198.
9. Efeyan A., Comb W.C., Sabatini D.M. Nutrient-sensing mechanisms and pathways. Nature 2015, 517:302-310.
10. Bar-Peled L., Schweitzer L.D., Zoncu R., Sabatini D.M. Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1. Cell 2012, 150:1196-1208.
11. Zoncu R., Bar-Peled L., Efeyan A., Wang S., Sancak Y., Sabatini D.M. mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase. Science 2011, 334:678-683.
12. Rebsamen M., Pochini L., Stasyk T., de Araujo M.E., Galluccio M., Kandasamy R.K., Snijder B., Fauster A., Rudashevskaya E.L., Bruckner M., Scorzoni S., Filipek P.A., Huber K.V., Bigenzahn J.W., Heinz L.X., Kraft C., Bennett K.L., Indiveri C., Huber L.A., Superti-Furga G. SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1. Nature 2015, 519:477-481.
13. Wang S., Tsun Z.Y., Wolfson R.L., Shen K., Wyant G.A., Plovanich M.E., Yuan E.D., Jones T.D., Chantranupong L., Comb W., Wang T., Bar-Peled L., Zoncu R., Straub C., Kim C., Park J., Sabatini B.L., Sabatini D.M. Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1. Science 2015, 347:188-194.
14. Bar-Peled L., Chantranupong L., Cherniack A.D., Chen W.W., Ottina K.A., Grabiner B.C., Spear E.D., Carter S.L., Meyerson M., Sabatini D.M. A tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1. Science 2013, 340:1100-1106.
15. Saxton R.A., Knockenhauer K.E., Wolfson R.L., Chantranupong L., Pacold M.E., Wang T., Schwartz T.U., Sabatini D.M. Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway. Science 2015.
16. Wolfson R.L., Chantranupong L., Saxton R.A., Shen K., Scaria S.M., Cantor J.R., Sabatini D.M. Sestrin2 is a leucine sensor for the mTORC1 pathway. Science 2015.
17. 13C]leucine. Clin. Sci. 1989, 76:447-454.
18. Jung J., Genau H.M., Behrends C. Amino acid-dependent mTORC1 regulation by the lysosomal membrane protein SLC38A9. Mol. Cell. Biol. 2015, 35:2479-2494.
19. Gordon B.S., Kazi A.A., Coleman C.S., Dennis M.D., Chau V., Jefferson L.S., Kimball S.R. RhoA modulates signaling through the mechanistic target of rapamycin complex 1 (mTORC1) in mammalian cells. Cell. Signal. 2014, 26:461-467.
20. Anthony J.C., Reiter A.K., Anthony T.G., Crozier S.J., Lang C.H., MacLean D.A., Kimball S.R., Jefferson L.S. Orally administered leucine enhances protein synthesis in skeletal muscle of diabetic rats in the absence of increases in 4E-BP1 or S6K1 phosphorylation. Diabetes 2002, 51:928-936.
21. Ye J., Palm W., Peng M., King B., Lindsten T., Li M.O., Koumenis C., Thompson C.B. GCN2 sustains mTORC1 suppression upon amino acid deprivation by inducing Sestrin2. Genes Dev. 2015, 29:2331-2336.
22. Dennis M.D., Baum J.I., Kimball S.R., Jefferson L.S. Mechanisms involved in the coordinate regulation of mTORC1 by insulin and amino acids. J. Biol. Chem. 2011, 286:8287-8296.
23. Winter J.N., Jefferson L.S., Kimball S.R. ERK and Akt signaling pathways function through parallel mechanisms to promote mTORC1 signaling. Am. J. Phys. 2011, 300:C1172-C1180.
24. Nicklin P., Bergman P., Zhang B., Triantafellow E., Wang H., Nyfeler B., Yang H., Hild M., Kung C., Wilson C., Myer V.E., MacKeigan J.P., Porter J.A., Wang Y.K., Cantley L.C., Finan P.M., Murphy L.O. Bidirectional transport of amino acids regulates mTOR and autophagy. Cell 2009, 136:521-534.
25. Ro S.H., Semple I.A., Park H., Park H., Park H.W., Kim M., Kim J.S., Lee J.H. Sestrin2 promotes Unc-51-like kinase 1 mediated phosphorylation of p62/sequestosome-1. FEBS J. 2014, 281:3816-3827.
26. Chan E.Y. mTORC1 phosphorylates the ULK1-mAtg13-FIP200 autophagy regulatory complex. Sci. Signal. 2009, 2:pe51.
27. Egan D.F., Kim J., Shaw R.J., Guan K.-L. The autophagy initiating kinase ULK1 is regulated via opposing phosphorylation by AMPK and mTOR. Autophagy 2011, 7:645-646.
28. Kim Y.C., Guan K.-L. mTOR: a pharmacologic target for autophagy regulation. J. Clin. Invest. 2015, 125:25-32.
29. Wong P.M., Feng Y., Wang J., Shi R., Jiang X. Regulation of autophagy by coordinated action of mTORC1 and protein phosphatase 2 A. Nat. Commun. 2015, 6:8048.
30. Bonfils G., Jaquenoud M., Bontron S., Ostrowicz C., Ungermann C., De Virgilio C. Leucyl-tRNA synthetase controls TORC1 via the EGO complex. Mol. Cell 2012, 46:105-110.
31. Han J.M., Jeong S.J., Park M.C., Kim G., Kwon N.H., Kim H.K., Ha S.H., Ryu S.H., Kim S. Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway. Cell 2012, 149:410-424.
32. Tischler M.E., Desautels M., Goldberg A.L. Does leucine, leucyl-tRNA, or some metabolite of leucine regulate protein synthesis in skeletal and cardiac muscle?. J. Biol. Chem. 1982, 257:1613-1621.
33. Adibi S.A., Modesto T.A., Morse E.L., Amin P.M. Amino acid levels in plasma, liver, and skeletal muscle during protein deprivation. Am. J. Phys. 1973, 225:408-414.
34. Kim H., An S., Ro S.H., Teixeira F., Jin Park G., Kim C., Cho C.S., Kim J.S., Jakob U., Hee Lee J., Cho U.S. Janus-faced Sestrin2 controls ROS and mTOR signalling through two separate functional domains. Nat. Commun. 2015, 6:10025.