Jewell Lab

Inhibition of Phosphodiesterase 4D suppresses mTORC1 signaling and pancreatic cancer growth.
Jeong MH, Urquhart G, Lewis C, Chi Z, Jewell JL.
JCI Insight. 2023 Jul 10;8(13):e158098. doi: 10.1172/jci.insight.158098.
PMID: 37427586

Manuscript Highlights
Featured in JCI This Month (for August).
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Regulation of mTORC1 by the Rag GTPases
Lama-Sherpa TD, Jeong MH, Jewell JL.
Biochem Soc Trans. 2023 Apr 26;51(2):655-664. doi: 10.1042/BST20210038.
PMID: 36929165

SNAT7 regulates mTORC1 via macropinocytosis.
Meng D, Yang Q, Jeong MH, Curukovic A, Tiwary S, Melick CH, Lama-Sherpa TD, Wang H, Huerta-Rosario M, Urquhart G, Zacharias LG, Lewis C, DeBerardinis RJ, Jewell JL.
PNAS. 2022 May 17;119(20):e2123261119. doi: 10.1073/pnas.2123261119.
PMID: 35561222

G-Protein Coupled Receptor Signaling and Mammalian Target of Rapamysin Complex 1 Regulation.
Melick CH, Lama-Sherpa TD, Curukovic A, Jewell JL.
Mol Pharmacol. 2022 Apr;101(4):181-190. doi: 10.1124/molpharm.121.000302.
PMID: 34965982

AKAP13 couples GPCR signaling to mTORC1 inhibition.
Zhang S, Wang H, Melick CH, Jeong MH, Curukovic A, Tiwary S, Lama-Sherpa TD, Meng D, Servage KA, James NG, Jewell JL.
PLoS Genet. 2021 Oct 21;17(10);e1009832. doi: 10.1371/journal.pgen.1009832.
PMID: 34673774

ArfGAP1 inhibits mTORC1 lysosomal localization and activation.
Meng D, Yang Q, Melick CH, Park BC, Hsieh T, Curukovic A, Jeong M, Zhang J, James NG, Jewell JL.
EMBO J. 2021 May 14;e106412. doi: 10.15252/embj.2020106412.
PMID: 33988249

RAG-ulating mTORC1 with amino acids.
Jewell JL
Nat Rev Mol Cell Biol. 2021 May 4. doi: 10.1038/s41580-021-00378-2
PMID: 33948014

Regulation of mTORC1 by Upstream Stimuli.
Melick CH, Jewell JL.
Genes (Basel). 2020 Aug 25;11(9):989. doi: 10.3390/genes11090989.
PMID: 32854217

Small molecule H89 renders the phosphorylation of S6K1 and AKT resistant to mTOR inhibitors.
Melick CH, Jewell JL.
Biochem J. 2020 May 29;477(10):1847-1863. doi: 10.1042/BCJ20190958.
PMID: 32347294

A-kinase anchoring protein 8L interacts with mTORC1 and promotes cell growth.
Melick CH, Mend D, Jewell JL.
J Biol Chem. 2020 Jun 5;295(23):8096-8105. doi: 10.1074/jbc.AC120.012595.Epub 2020 Apr 20.
PMID: 32312749

Glutamine and asparagine activate mTORC1 independently of Rag GTPases.
Meng D, Yang Q, Wang H, Melick CH, Navlani R, Frank AR, Jewell JL.
J Biol Chem. 2020 Mar 6;295(10):2890-2899. doi: 10.1074/jbc.AC119.011578.Epub 2020 Feb 4.
PMID: 32019866

Manuscript Highlights
Highlighted in the 19th amendment issue
Editors’ Pick
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Amino Acid Sensing: Architecture of mTORC1 on the Lysosome Surface.
Peng W, Jewell JL.
Curr Biol. 2020 Jan 20;30(2):R89-R91. doi: 10.1016/j.cub.2019.11.087.
PMID: 31962086

Clearing debris.
Meng D, Jewell JL
Nat Chem Biol. 2019 Aug;15(8):760-761. doi: 10.1038/s41589-019-0320-8.
PMID: 31285594

GPCR signaling inhibits mTORC1 via PKA phosphorylation of Raptor.
Jewell JL, Fu V, Hong AW, Yu FX, Meng D, Melick CH, Wang H, Lam WM, Yuan HX, Taylor SS, Guan KL.
Elife. 2019 May 21;8. pii: e43038. doi: 10.7554/eLife.43038.
PMID: 31112131

mTOR signaling in stem and progenitor cells.
Meng D, Frank AR, Jewell JL.
Development. 2018 Jan 8;145(1). pii: dev152595. doi: 10.1242/dev.152595. Review.
PMID: 29311260

Amino acid and small GTPase regulation of mTORC1.
Nguyen TP, Frank AR, Jewell JL.
Cell Logist. 2017 Sep 29;7(4):e1378794. doi: 10.1080/21592799.2017.1378794. eCollection 2017. Review.
PMID: 29296509

NLK phosphorylates Raptor to mediate stress-induced mTORC1 inhibition.
Yuan HX, Wang Z, Yu FX, Li F, Russell RC, Jewell JL, Guan KL.
Genes Dev. 2015 Nov 15;29(22):2362-76. doi: 10.1101/gad.265116.115.
PMID: 26588989

Micro(RNA) managing by mTORC1.
Jewell JL, Flores F, Guan KL.
Mol Cell. 2015 Feb 19;57(4):575-576. doi: 10.1016/j.molcel.2015.02.006.
PMID: 25699705

Metabolism. Differential regulation of mTORC1 by leucine and glutamine.
Jewell JL, Kim YC, Russell RC, Yu FX, Park HW, Plouffe SW, Tagliabracci VS, Guan KL.
Science. 2015 Jan 9;347(6218):194-8. doi: 10.1126/science.1259472. Epub 2015 Jan 7.
PMID: 25567907

Rag GTPases are cardioprotective by regulating lysosomal function.
Kim YC, Park HW, Sciarretta S, Mo JS, Jewell JL, Russell RC, Wu X, Sadoshima J, Guan KL.
Nat Commun. 2014 Jul 1;5:4241. doi: 10.1038/ncomms5241.
PMID: 24980141

Protein kinase A activates the Hippo pathway to modulate cell proliferation and differentiation.
Yu FX, Zhang Y, Park HW, Jewell JL, Chen Q, Deng Y, Pan D, Taylor SS, Lai ZC, Guan KL.
Genes Dev. 2013 Jun 1;27(11):1223-32. doi: 10.1101/gad.219402.113.
PMID: 23752589

Nutrient signaling to mTOR and cell growth.
Jewell JL, Guan KL.
Trends Biochem Sci. 2013 May;38(5):233-42. doi: 10.1016/j.tibs.2013.01.004. Epub 2013 Mar 1. Review.
PMID: 23465396

Amino acid signalling upstream of mTOR.
Jewell JL, Russell RC, Guan KL.
Nat Rev Mol Cell Biol. 2013 Mar;14(3):133-9. doi: 10.1038/nrm3522. Epub 2013 Jan 30. Review.
PMID: 23361334

Regulation of the Hippo-YAP pathway by G-protein-coupled receptor signaling.
Yu FX, Zhao B, Panupinthu N, Jewell JL, Lian I, Wang LH, Zhao J, Yuan H, Tumaneng K, Li H, Fu XD, Mills GB, Guan KL.
Cell. 2012 Aug 17;150(4):780-91. doi: 10.1016/j.cell.2012.06.037. Epub 2012 Aug 2.
PMID: 22863277

Munc18c phosphorylation by the insulin receptor links cell signaling directly to SNARE exocytosis.
Jewell JL, Oh E, Ramalingam L, Kalwat MA, Tagliabracci VS, Tackett L, Elmendorf JS, and Thurmond DC.
J Cell Biol. 2011 Apr 4;193(1):185-99. doi: 10.1083/jcb.201007176.Epub 2011 Mar 28.
PMID: 21444687

Exocytosis mechanisms underlying insulin release and glucose uptake: conserved roles for Munc18c and syntaxin 4.
Jewell JL, Oh E, Thurmond DC.
Am J Physiol Regul Integr Comp Physiol. 2010 Mar;298(3):R517-31. doi: 10.1152/ajpregu.00597.2009.Epub 2010 Jan 6.
PMID: 20053958

The tyrosine phosphorylation of Munc18c induces a switch in binding specificity from syntaxin 4 to Doc2beta.
Jewell JL, Oh E, Bennett SM, Meroueh SO, Thurmond DC.
J Biol Chem. 2008 Aug 1;283(31):21734-46. doi: 10.1074/jbc.M710445200. Epub 2008 Jun 9.
PMID: 18541526

Filamentous actin regulates insulin exocytosis through direct interaction with Syntaxin 4.
Jewell JL, Luo W, Oh E, Wang Z, Thurmond DC.
J Biol Chem. 2008 Apr 18;283(16):10716-26. doi: 10.1074/jbc.M709876200. Epub 2008 Feb 19.
PMID: 18285343