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HIV-1 Nef dimers short-circuit immune receptor signaling by activating Tec-family kinases at the host cell membrane.

Li WF, Aryal M, Shu ST, Smithgall TE.

J Biol Chem. 2020 Mar 6. pii: jbc.RA120.012536. doi: 10.1074/jbc.RA120.012536. [Epub ahead of print]


Discovery of Non-peptide Small Molecule Allosteric Modulators of the Src-family Kinase, Hck.

Dorman HR, Close D, Wingert BM, Camacho CJ, Johnston PA, Smithgall TE.

Front Chem. 2019 Nov 28;7:822. doi: 10.3389/fchem.2019.00822. eCollection 2019.


Expression of myeloid Src-family kinases is associated with poor prognosis in AML and influences Flt3-ITD kinase inhibitor acquired resistance.

Patel RK, Weir MC, Shen K, Snyder D, Cooper VS, Smithgall TE.

PLoS One. 2019 Dec 2;14(12):e0225887. doi: 10.1371/journal.pone.0225887. eCollection 2019.


Tight-Binding Hydroxypyrazole HIV-1 Nef Inhibitors Suppress Viral Replication in Donor Mononuclear Cells and Reverse Nef-Mediated MHC-I Downregulation.

Shi H, Tice CM, Emert-Sedlak L, Chen L, Li WF, Carlsen M, Wrobel JE, Reitz AB, Smithgall TE.

ACS Infect Dis. 2020 Feb 14;6(2):302-312. doi: 10.1021/acsinfecdis.9b00382. Epub 2019 Dec 16.


Molecular basis for the interaction between human choline kinase alpha and the SH3 domain of the c-Src tyrosine kinase.

Kall SL, Whitlatch K, Smithgall TE, Lavie A.

Sci Rep. 2019 Nov 19;9(1):17121. doi: 10.1038/s41598-019-53447-0.


The Src family kinase Fgr is a transforming oncoprotein that functions independently of SH3-SH2 domain regulation.

Shen K, Moroco JA, Patel RK, Shi H, Engen JR, Dorman HR, Smithgall TE.

Sci Signal. 2018 Oct 23;11(553). pii: eaat5916. doi: 10.1126/scisignal.aat5916.


Selective Inhibition of the Myeloid Src-Family Kinase Fgr Potently Suppresses AML Cell Growth in Vitro and in Vivo.

Weir MC, Shu ST, Patel RK, Hellwig S, Chen L, Tan L, Gray NS, Smithgall TE.

ACS Chem Biol. 2018 Jun 15;13(6):1551-1559. doi: 10.1021/acschembio.8b00154. Epub 2018 May 30.


HIV-1 Nef Antagonizes SERINC5 Restriction by Downregulation of SERINC5 via the Endosome/Lysosome System.

Shi J, Xiong R, Zhou T, Su P, Zhang X, Qiu X, Li H, Li S, Yu C, Wang B, Ding C, Smithgall TE, Zheng YH.

J Virol. 2018 May 14;92(11). pii: e00196-18. doi: 10.1128/JVI.00196-18. Print 2018 Jun 1.


A single β-octyl glucoside molecule induces HIV-1 Nef dimer formation in the absence of partner protein binding.

Wu M, Alvarado JJ, Augelli-Szafran CE, Ptak RG, Smithgall TE.

PLoS One. 2018 Feb 7;13(2):e0192512. doi: 10.1371/journal.pone.0192512. eCollection 2018. Erratum in: PLoS One. 2018 Apr 17;13(4):e0196229.


Remodeling of HIV-1 Nef Structure by Src-Family Kinase Binding.

Moroco JA, Alvarado JJ, Staudt RP, Shi H, Wales TE, Smithgall TE, Engen JR.

J Mol Biol. 2018 Feb 2;430(3):310-321. doi: 10.1016/j.jmb.2017.12.008. Epub 2017 Dec 16.


Pharmacologic HIV-1 Nef blockade promotes CD8 T cell-mediated elimination of latently HIV-1-infected cells in vitro.

Mujib S, Saiyed A, Fadel S, Bozorgzad A, Aidarus N, Yue FY, Benko E, Kovacs C, Emert-Sedlak LA, Smithgall TE, Ostrowski MA.

JCI Insight. 2017 Sep 7;2(17). pii: 93684. doi: 10.1172/jci.insight.93684. eCollection 2017 Sep 7.


Csk-homologous kinase (Chk) is an efficient inhibitor of Src-family kinases but a poor catalyst of phosphorylation of their C-terminal regulatory tyrosine.

Advani G, Lim YC, Catimel B, Lio DSS, Ng NLY, Chüeh AC, Tran M, Anasir MI, Verkade H, Zhu HJ, Turk BE, Smithgall TE, Ang CS, Griffin M, Cheng HC.

Cell Commun Signal. 2017 Aug 7;15(1):29. doi: 10.1186/s12964-017-0186-x.


Dual inhibition of Fes and Flt3 tyrosine kinases potently inhibits Flt3-ITD+ AML cell growth.

Weir MC, Hellwig S, Tan L, Liu Y, Gray NS, Smithgall TE.

PLoS One. 2017 Jul 20;12(7):e0181178. doi: 10.1371/journal.pone.0181178. eCollection 2017.


Nek7 Protects Telomeres from Oxidative DNA Damage by Phosphorylation and Stabilization of TRF1.

Tan R, Nakajima S, Wang Q, Sun H, Xue J, Wu J, Hellwig S, Zeng X, Yates NA, Smithgall TE, Lei M, Jiang Y, Levine AS, Su B, Lan L.

Mol Cell. 2017 Mar 2;65(5):818-831.e5. doi: 10.1016/j.molcel.2017.01.015. Epub 2017 Feb 16.


Cell-based Fluorescence Complementation Reveals a Role for HIV-1 Nef Protein Dimerization in AP-2 Adaptor Recruitment and CD4 Co-receptor Down-regulation.

Shu ST, Emert-Sedlak LA, Smithgall TE.

J Biol Chem. 2017 Feb 17;292(7):2670-2678. doi: 10.1074/jbc.M116.770016. Epub 2016 Dec 28.


c-Abl Tyrosine Kinase Adopts Multiple Active Conformational States in Solution.

Badger J, Grover P, Shi H, Panjarian SB, Engen JR, Smithgall TE, Makowski L.

Biochemistry. 2016 Jun 14;55(23):3251-60. doi: 10.1021/acs.biochem.6b00202. Epub 2016 Jun 3.


Hydrogen Exchange Mass Spectrometry of Related Proteins with Divergent Sequences: A Comparative Study of HIV-1 Nef Allelic Variants.

Wales TE, Poe JA, Emert-Sedlak L, Morgan CR, Smithgall TE, Engen JR.

J Am Soc Mass Spectrom. 2016 Jun;27(6):1048-61. doi: 10.1007/s13361-016-1365-5. Epub 2016 Mar 31.


Synthesis and evaluation of orally active small molecule HIV-1 Nef antagonists.

Emert-Sedlak LA, Loughran HM, Shi H, Kulp JL 3rd, Shu ST, Zhao J, Day BW, Wrobel JE, Reitz AB, Smithgall TE.

Bioorg Med Chem Lett. 2016 Mar 1;26(5):1480-1484. doi: 10.1016/j.bmcl.2016.01.043. Epub 2016 Jan 21.


Dynamics of the Tec-family tyrosine kinase SH3 domains.

Roberts JM, Tarafdar S, Joseph RE, Andreotti AH, Smithgall TE, Engen JR, Wales TE.

Protein Sci. 2016 Apr;25(4):852-64. doi: 10.1002/pro.2887. Epub 2016 Mar 18.


Subtle Dynamic Changes Accompany Hck Activation by HIV-1 Nef and are Reversed by an Antiretroviral Kinase Inhibitor.

Wales TE, Hochrein JM, Morgan CR, Emert-Sedlak LA, Smithgall TE, Engen JR.

Biochemistry. 2015 Oct 20;54(41):6382-91. doi: 10.1021/acs.biochem.5b00875. Epub 2015 Oct 6.


MCPIP1 Endoribonuclease Activity Negatively Regulates Interleukin-17-Mediated Signaling and Inflammation.

Garg AV, Amatya N, Chen K, Cruz JA, Grover P, Whibley N, Conti HR, Hernandez Mir G, Sirakova T, Childs EC, Smithgall TE, Biswas PS, Kolls JK, McGeachy MJ, Kolattukudy PE, Gaffen SL.

Immunity. 2015 Sep 15;43(3):475-87. doi: 10.1016/j.immuni.2015.07.021. Epub 2015 Aug 25.


Fluorescence Polarization Screening Assays for Small Molecule Allosteric Modulators of ABL Kinase Function.

Grover P, Shi H, Baumgartner M, Camacho CJ, Smithgall TE.

PLoS One. 2015 Jul 29;10(7):e0133590. doi: 10.1371/journal.pone.0133590. eCollection 2015.


Membrane-Associated Conformation of HIV-1 Nef Investigated with Hydrogen Exchange Mass Spectrometry at a Langmuir Monolayer.

Pirrone GF, Emert-Sedlak LA, Wales TE, Smithgall TE, Kent MS, Engen JR.

Anal Chem. 2015 Jul 21;87(14):7030-5. doi: 10.1021/acs.analchem.5b01725. Epub 2015 Jul 2.


A Discovery Strategy for Selective Inhibitors of c-Src in Complex with the Focal Adhesion Kinase SH3/SH2-binding Region.

Moroco JA, Baumgartner MP, Rust HL, Choi HG, Hur W, Gray NS, Camacho CJ, Smithgall TE.

Chem Biol Drug Des. 2015 Aug;86(2):144-55. doi: 10.1111/cbdd.12473. Epub 2014 Nov 28.


Src-family tyrosine kinase activities are essential for differentiation of human embryonic stem cells.

Zhang X, Simerly C, Hartnett C, Schatten G, Smithgall TE.

Stem Cell Res. 2014 Nov;13(3 Pt A):379-89. doi: 10.1016/j.scr.2014.09.007. Epub 2014 Sep 30.


Differential sensitivity of Src-family kinases to activation by SH3 domain displacement.

Moroco JA, Craigo JK, Iacob RE, Wales TE, Engen JR, Smithgall TE.

PLoS One. 2014 Aug 21;9(8):e105629. doi: 10.1371/journal.pone.0105629. eCollection 2014.


Interaction with the Src homology (SH3-SH2) region of the Src-family kinase Hck structures the HIV-1 Nef dimer for kinase activation and effector recruitment.

Alvarado JJ, Tarafdar S, Yeh JI, Smithgall TE.

J Biol Chem. 2014 Oct 10;289(41):28539-53. doi: 10.1074/jbc.M114.600031. Epub 2014 Aug 13.


Human trophoblasts confer resistance to viruses implicated in perinatal infection.

Bayer A, Delorme-Axford E, Sleigher C, Frey TK, Trobaugh DW, Klimstra WB, Emert-Sedlak LA, Smithgall TE, Kinchington PR, Vadia S, Seveau S, Boyle JP, Coyne CB, Sadovsky Y.

Am J Obstet Gynecol. 2015 Jan;212(1):71.e1-71.e8. doi: 10.1016/j.ajog.2014.07.060. Epub 2014 Aug 6.


The accessory factor Nef links HIV-1 to Tec/Btk kinases in an Src homology 3 domain-dependent manner.

Tarafdar S, Poe JA, Smithgall TE.

J Biol Chem. 2014 May 30;289(22):15718-28. doi: 10.1074/jbc.M114.572099. Epub 2014 Apr 10.


Synthesis and structure-activity analysis of diphenylpyrazolodiazene inhibitors of the HIV-1 Nef virulence factor.

Iyer PC, Zhao J, Emert-Sedlak LA, Moore KK, Smithgall TE, Day BW.

Bioorg Med Chem Lett. 2014 Apr 1;24(7):1702-6. doi: 10.1016/j.bmcl.2014.02.045. Epub 2014 Feb 26.


Small molecule inhibitors of the HIV-1 virulence factor, Nef.

Smithgall TE, Thomas G.

Drug Discov Today Technol. 2013 Dec;10(4):e523-9. doi: 10.1016/j.ddtec.2013.07.002. Review.


Development and validation of a high-content bimolecular fluorescence complementation assay for small-molecule inhibitors of HIV-1 Nef dimerization.

Poe JA, Vollmer L, Vogt A, Smithgall TE.

J Biomol Screen. 2014 Apr;19(4):556-65. doi: 10.1177/1087057113513640. Epub 2013 Nov 26.


Discovery of a diaminoquinoxaline benzenesulfonamide antagonist of HIV-1 Nef function using a yeast-based phenotypic screen.

Trible RP, Narute P, Emert-Sedlak LA, Alvarado JJ, Atkins K, Thomas L, Kodama T, Yanamala N, Korotchenko V, Day BW, Thomas G, Smithgall TE.

Retrovirology. 2013 Nov 14;10:135. doi: 10.1186/1742-4690-10-135.


Formation of a unique cluster of G-quadruplex structures in the HIV-1 Nef coding region: implications for antiviral activity.

Perrone R, Nadai M, Poe JA, Frasson I, Palumbo M, Palù G, Smithgall TE, Richter SN.

PLoS One. 2013 Aug 27;8(8):e73121. doi: 10.1371/journal.pone.0073121. eCollection 2013.


c-Yes tyrosine kinase is a potent suppressor of ES cell differentiation and antagonizes the actions of its closest phylogenetic relative, c-Src.

Zhang X, Meyn MA 3rd, Smithgall TE.

ACS Chem Biol. 2014 Jan 17;9(1):139-46. doi: 10.1021/cb400249b. Epub 2013 Aug 15.


A dynamic G-quadruplex region regulates the HIV-1 long terminal repeat promoter.

Perrone R, Nadai M, Frasson I, Poe JA, Butovskaya E, Smithgall TE, Palumbo M, Palù G, Richter SN.

J Med Chem. 2013 Aug 22;56(16):6521-30. doi: 10.1021/jm400914r. Epub 2013 Aug 6.


Partial cooperative unfolding in proteins as observed by hydrogen exchange mass spectrometry.

Engen JR, Wales TE, Chen S, Marzluff EM, Hassell KM, Weis DD, Smithgall TE.

Int Rev Phys Chem. 2013 Jan 1;32(1):96-127.


Effector kinase coupling enables high-throughput screens for direct HIV-1 Nef antagonists with antiretroviral activity.

Emert-Sedlak LA, Narute P, Shu ST, Poe JA, Shi H, Yanamala N, Alvarado JJ, Lazo JS, Yeh JI, Johnston PA, Smithgall TE.

Chem Biol. 2013 Jan 24;20(1):82-91. doi: 10.1016/j.chembiol.2012.11.005.


Structure and dynamic regulation of Abl kinases.

Panjarian S, Iacob RE, Chen S, Engen JR, Smithgall TE.

J Biol Chem. 2013 Feb 22;288(8):5443-50. doi: 10.1074/jbc.R112.438382. Epub 2013 Jan 11. Review.


Enhanced SH3/linker interaction overcomes Abl kinase activation by gatekeeper and myristic acid binding pocket mutations and increases sensitivity to small molecule inhibitors.

Panjarian S, Iacob RE, Chen S, Wales TE, Engen JR, Smithgall TE.

J Biol Chem. 2013 Mar 1;288(9):6116-29. doi: 10.1074/jbc.M112.431312. Epub 2013 Jan 9.


Individual Src-family tyrosine kinases direct the degradation or protection of the clock protein Timeless via differential ubiquitylation.

O'Reilly LP, Zhang X, Smithgall TE.

Cell Signal. 2013 Apr;25(4):860-6. doi: 10.1016/j.cellsig.2012.12.009. Epub 2012 Dec 22.


Small-molecule inhibitors of the c-Fes protein-tyrosine kinase.

Hellwig S, Miduturu CV, Kanda S, Zhang J, Filippakopoulos P, Salah E, Deng X, Choi HG, Zhou W, Hur W, Knapp S, Gray NS, Smithgall TE.

Chem Biol. 2012 Apr 20;19(4):529-40. doi: 10.1016/j.chembiol.2012.01.020.


HIV-1 Nef interaction influences the ATP-binding site of the Src-family kinase, Hck.

Pene-Dumitrescu T, Shu ST, Wales TE, Alvarado JJ, Shi H, Narute P, Moroco JA, Yeh JI, Engen JR, Smithgall TE.

BMC Chem Biol. 2012 Mar 15;12:1. doi: 10.1186/1472-6769-12-1.


Nef alleles from all major HIV-1 clades activate Src-family kinases and enhance HIV-1 replication in an inhibitor-sensitive manner.

Narute PS, Smithgall TE.

PLoS One. 2012;7(2):e32561. doi: 10.1371/journal.pone.0032561. Epub 2012 Feb 29.


The contrasting oncogenic and tumor suppressor roles of FES.

Greer PA, Kanda S, Smithgall TE.

Front Biosci (Schol Ed). 2012 Jan 1;4:489-501. Review.


Phosphotyrosine-dependent coupling of Tim-3 to T-cell receptor signaling pathways.

Lee J, Su EW, Zhu C, Hainline S, Phuah J, Moroco JA, Smithgall TE, Kuchroo VK, Kane LP.

Mol Cell Biol. 2011 Oct;31(19):3963-74. doi: 10.1128/MCB.05297-11. Epub 2011 Aug 1.


On the solution conformation and dynamics of the HIV-1 viral infectivity factor.

Marcsisin SR, Narute PS, Emert-Sedlak LA, Kloczewiak M, Smithgall TE, Engen JR.

J Mol Biol. 2011 Jul 29;410(5):1008-22. doi: 10.1016/j.jmb.2011.04.053.


Structure and regulation of the c-Fes protein-tyrosine kinase.

Hellwig S, Smithgall TE.

Front Biosci (Landmark Ed). 2011 Jun 1;16:3146-55. Review.


An unexpected role for the clock protein timeless in developmental apoptosis.

O'Reilly LP, Watkins SC, Smithgall TE.

PLoS One. 2011 Feb 17;6(2):e17157. doi: 10.1371/journal.pone.0017157.


Crystal structure of the Src family kinase Hck SH3-SH2 linker regulatory region supports an SH3-dominant activation mechanism.

Alvarado JJ, Betts L, Moroco JA, Smithgall TE, Yeh JI.

J Biol Chem. 2010 Nov 12;285(46):35455-61. doi: 10.1074/jbc.M110.145102. Epub 2010 Sep 1.

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