Scholars@Duke

• Background
• 

  Education, Training, & Certifications

  • Ph.D., Duke University 2002
• 

  Previous Appointments & Affiliations

  • Assistant Professor in Medicine, Medicine, Cardiology, Medicine 2008 - 2020
• Research
• 

  Selected Grants

  • Molecular Regulation of Cardiovascular 7 TM Receptors awarded by National Institutes of Health 1976 - 2023
  • B-Arrestins and G Protein-Coupled Receptor Kinases in Cardiovascular Function awarded by National Institutes of Health 2002 - 2012
• 

  External Relationships

  • Amgen, Inc.
  • Third Rock Ventures - Septerna, Inc.
• Publications & Artistic Works
• 

  Selected Publications

  • Academic Articles

    • Li, Angus, Samuel Liu, Rennica Huang, Seungkirl Ahn, and Robert J. Lefkowitz. “Loss of Biased Signaling Specificity of the Angiotensin II Type 1 Receptor in Overexpressed Systems.” Faseb J 36 Suppl 1 (May 2022). https://doi.org/10.1096/fasebj.2022.36.S1.R2797.
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    • Wang, Jialu, Biswaranjan Pani, Ilhan Gokhan, Xinyu Xiong, Alem W. Kahsai, Haoran Jiang, Seungkirl Ahn, Robert J. Lefkowitz, and Howard A. Rockman. “β-Arrestin-Biased Allosteric Modulator Potentiates Carvedilol-Stimulated β Adrenergic Receptor Cardioprotection.” Mol Pharmacol 100, no. 6 (December 2021): 568–79. https://doi.org/10.1124/molpharm.121.000359.
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    • “Correction to "Unique Positive Cooperativity Between the β-Arrestin-Biased β-Blocker Carvedilol and a Small Molecule Positive Allosteric Modulator of the β2-Adrenergic Receptor".” Mol Pharmacol 100, no. 6 (December 2021): 597. https://doi.org/10.1124/molpharm.121.000363err.
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    • Pani, Biswaranjan, Seungkirl Ahn, Paula K. Rambarat, Shashank Vege, Alem W. Kahsai, Andrew Liu, Bruno N. Valan, Dean P. Staus, Tommaso Costa, and Robert J. Lefkowitz. “Unique Positive Cooperativity Between the β-Arrestin-Biased β-Blocker Carvedilol and a Small Molecule Positive Allosteric Modulator of the β2-Adrenergic Receptor.” Mol Pharmacol 100, no. 5 (November 2021): 513–25. https://doi.org/10.1124/molpharm.121.000363.
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    • Pani, B., S. Ahn, P. K. Rambarfat, S. Vege, A. W. Kahsai, A. Liu, B. N. Valan, D. P. Status, T. Costa, and R. J. Lefkowitz. “Unique Positive Cooperativity Between the beta-Arrestin-Biased beta-Blocker Carvedilol and a Small Molecule Positive Allosteric Modulator of the beta 2-Adrenergic Receptor (vol 100, pg 513, 2021).” Molecular Pharmacology 100, no. 6 (2021): 597–597.
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    • Ahn, Seungkirl, Sudha K. Shenoy, Louis M. Luttrell, and Robert J. Lefkowitz. “SnapShot: β-Arrestin Functions.” Cell 182, no. 5 (September 3, 2020): 1362-1362.e1. https://doi.org/10.1016/j.cell.2020.07.034.
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    • Liu, Xiangyu, Ali Masoudi, Alem W. Kahsai, Li-Yin Huang, Biswaranjan Pani, Dean P. Staus, Paul J. Shim, et al. “Mechanism of β2AR regulation by an intracellular positive allosteric modulator.” Science 364, no. 6447 (June 28, 2019): 1283–87. https://doi.org/10.1126/science.aaw8981.
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    • Luttrell, Louis M., Jialu Wang, Bianca Plouffe, Jeffrey S. Smith, Lama Yamani, Suneet Kaur, Pierre-Yves Jean-Charles, et al. “Manifold roles of β-arrestins in GPCR signaling elucidated with siRNA and CRISPR/Cas9.” Sci Signal 11, no. 549 (September 25, 2018). https://doi.org/10.1126/scisignal.aat7650.
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    • Choi, Minjung, Dean P. Staus, Laura M. Wingler, Seungkirl Ahn, Biswaranjan Pani, William D. Capel, and Robert J. Lefkowitz. “G protein-coupled receptor kinases (GRKs) orchestrate biased agonism at the β2-adrenergic receptor.” Sci Signal 11, no. 544 (August 21, 2018). https://doi.org/10.1126/scisignal.aar7084.
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    • Ahn, Seungkirl, Biswaranjan Pani, Alem W. Kahsai, Eva K. Olsen, Gitte Husemoen, Mikkel Vestergaard, Lei Jin, et al. “Small-Molecule Positive Allosteric Modulators of the β2-Adrenoceptor Isolated from DNA-Encoded Libraries.” Mol Pharmacol 94, no. 2 (August 2018): 850–61. https://doi.org/10.1124/mol.118.111948.
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    • Meng, Kaicheng, Paul Shim, Qingtin Wang, Shuai Zhao, Ting Gu, Alem W. Kahsai, Seungkirl Ahn, and Xin Chen. “Design, synthesis, and functional assessment of Cmpd-15 derivatives as negative allosteric modulators for the β2-adrenergic receptor.” Bioorg Med Chem 26, no. 9 (May 15, 2018): 2320–30. https://doi.org/10.1016/j.bmc.2018.03.023.
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    • Liu, Xiangyu, Seungkirl Ahn, Alem W. Kahsai, Kai-Cheng Meng, Naomi R. Latorraca, Biswaranjan Pani, A. J. Venkatakrishnan, et al. “Mechanism of intracellular allosteric β2AR antagonist revealed by X-ray crystal structure.” Nature 548, no. 7668 (August 24, 2017): 480–84. https://doi.org/10.1038/nature23652.
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    • Ahn, Seungkirl, Alem W. Kahsai, Biswaranjan Pani, Qin-Ting Wang, Shuai Zhao, Alissa L. Wall, Ryan T. Strachan, et al. “Allosteric "beta-blocker" isolated from a DNA-encoded small molecule library.” Proc Natl Acad Sci U S A 114, no. 7 (February 14, 2017): 1708–13. https://doi.org/10.1073/pnas.1620645114.
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    • Kahsai, Alem W., James W. Wisler, Jungmin Lee, Seungkirl Ahn, Thomas J. Cahill Iii, S Moses Dennison, Dean P. Staus, et al. “Conformationally selective RNA aptamers allosterically modulate the β2-adrenoceptor.” Nat Chem Biol 12, no. 9 (September 2016): 709–16. https://doi.org/10.1038/nchembio.2126.
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    • Staus, Dean P., Ryan T. Strachan, Aashish Manglik, Biswaranjan Pani, Alem W. Kahsai, Tae Hun Kim, Laura M. Wingler, et al. “Allosteric nanobodies reveal the dynamic range and diverse mechanisms of G-protein-coupled receptor activation.” Nature 535, no. 7612 (July 21, 2016): 448–52. https://doi.org/10.1038/nature18636.
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    • Strachan, Ryan T., Jin-peng Sun, David H. Rominger, Jonathan D. Violin, Seungkirl Ahn, Alex Rojas Bie Thomsen, Xiao Zhu, Andrew Kleist, Tommaso Costa, and Robert J. Lefkowitz. “Divergent transducer-specific molecular efficacies generate biased agonism at a G protein-coupled receptor (GPCR).” J Biol Chem 289, no. 20 (May 16, 2014): 14211–24. https://doi.org/10.1074/jbc.M114.548131.
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    • Staus, Dean P., Laura M. Wingler, Ryan T. Strachan, Soren G. F. Rasmussen, Els Pardon, Seungkirl Ahn, Jan Steyaert, Brian K. Kobilka, and Robert J. Lefkowitz. “Regulation of β2-adrenergic receptor function by conformationally selective single-domain intrabodies.” Mol Pharmacol 85, no. 3 (March 2014): 472–81. https://doi.org/10.1124/mol.113.089516.
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    • Aristotelous, Tonia, Seungkirl Ahn, Arun K. Shukla, Sylwia Gawron, Maria F. Sassano, Alem W. Kahsai, Laura M. Wingler, et al. “Discovery of β2 Adrenergic Receptor Ligands Using Biosensor Fragment Screening of Tagged Wild-Type Receptor.” Acs Med Chem Lett 4, no. 10 (October 10, 2013): 1005–10. https://doi.org/10.1021/ml400312j.
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    • Weiss, Dahlia R., SeungKirl Ahn, Maria F. Sassano, Andrew Kleist, Xiao Zhu, Ryan Strachan, Bryan L. Roth, Robert J. Lefkowitz, and Brian K. Shoichet. “Conformation guides molecular efficacy in docking screens of activated β-2 adrenergic G protein coupled receptor.” Acs Chem Biol 8, no. 5 (May 17, 2013): 1018–26. https://doi.org/10.1021/cb400103f.
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    • Wang, J., A. Seungkirl, A. W. Kahsai, R. Liu, J. Ren, K. Hu, X. Sun, and X. Chen. “Synthesis of β2-AR agonist BI-167107.” Chinese Journal of Organic Chemistry 33, no. 3 (March 1, 2013): 634–39. https://doi.org/10.6023/cjoc201211015.
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    • Heitzler, Domitille, Guillaume Durand, Nathalie Gallay, Aurélien Rizk, Seungkirl Ahn, Jihee Kim, Jonathan D. Violin, et al. “Competing G protein-coupled receptor kinases balance G protein and β-arrestin signaling.” Mol Syst Biol 8 (June 26, 2012): 590. https://doi.org/10.1038/msb.2012.22.
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    • Reiter, Eric, Seungkirl Ahn, Arun K. Shukla, and Robert J. Lefkowitz. “Molecular mechanism of β-arrestin-biased agonism at seven-transmembrane receptors.” Annu Rev Pharmacol Toxicol 52 (2012): 179–97. https://doi.org/10.1146/annurev.pharmtox.010909.105800.
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    • Rajagopal, Sudarshan, Seungkirl Ahn, David H. Rominger, William Gowen-MacDonald, Christopher M. Lam, Scott M. Dewire, Jonathan D. Violin, and Robert J. Lefkowitz. “Quantifying ligand bias at seven-transmembrane receptors.” Mol Pharmacol 80, no. 3 (September 2011): 367–77. https://doi.org/10.1124/mol.111.072801.
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    • Kahsai, Alem W., Kunhong Xiao, Sudarshan Rajagopal, Seungkirl Ahn, Arun K. Shukla, Jinpeng Sun, Terrence G. Oas, and Robert J. Lefkowitz. “Multiple ligand-specific conformations of the β2-adrenergic receptor.” Nat Chem Biol 7, no. 10 (August 21, 2011): 692–700. https://doi.org/10.1038/nchembio.634.
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    • Hara, Makoto R., Jeffrey J. Kovacs, Erin J. Whalen, Sudarshan Rajagopal, Ryan T. Strachan, Wayne Grant, Aaron J. Towers, et al. “A stress response pathway regulates DNA damage through β2-adrenoreceptors and β-arrestin-1.” Nature 477, no. 7364 (August 21, 2011): 349–53. https://doi.org/10.1038/nature10368.
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    • Nobles, Kelly N., Kunhong Xiao, Seungkirl Ahn, Arun K. Shukla, Christopher M. Lam, Sudarshan Rajagopal, Ryan T. Strachan, et al. “Distinct phosphorylation sites on the β(2)-adrenergic receptor establish a barcode that encodes differential functions of β-arrestin.” Sci Signal 4, no. 185 (August 9, 2011): ra51. https://doi.org/10.1126/scisignal.2001707.
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    • Shukla, Arun K., Jihee Kim, Seungkirl Ahn, Kunhong Xiao, Sudha K. Shenoy, Wolfgang Liedtke, and Robert J. Lefkowitz. “Arresting a transient receptor potential (TRP) channel: beta-arrestin 1 mediates ubiquitination and functional down-regulation of TRPV4.” J Biol Chem 285, no. 39 (September 24, 2010): 30115–25. https://doi.org/10.1074/jbc.M110.141549.
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    • Rajagopal, Sudarshan, Jihee Kim, Seungkirl Ahn, Stewart Craig, Christopher M. Lam, Norma P. Gerard, Craig Gerard, and Robert J. Lefkowitz. “Beta-arrestin- but not G protein-mediated signaling by the "decoy" receptor CXCR7.” Proc Natl Acad Sci U S A 107, no. 2 (January 12, 2010): 628–32. https://doi.org/10.1073/pnas.0912852107.
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    • Kim, Jihee, Seungkirl Ahn, Keshava Rajagopal, and Robert J. Lefkowitz. “Independent beta-arrestin2 and Gq/protein kinase Czeta pathways for ERK stimulated by angiotensin type 1A receptors in vascular smooth muscle cells converge on transactivation of the epidermal growth factor receptor.” J Biol Chem 284, no. 18 (May 1, 2009): 11953–62. https://doi.org/10.1074/jbc.M808176200.
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    • Shenoy, Sudha K., Aalok S. Modi, Arun K. Shukla, Kunhong Xiao, Magali Berthouze, Seungkirl Ahn, Keith D. Wilkinson, William E. Miller, and Robert J. Lefkowitz. “Beta-arrestin-dependent signaling and trafficking of 7-transmembrane receptors is reciprocally regulated by the deubiquitinase USP33 and the E3 ligase Mdm2.” Proc Natl Acad Sci U S A 106, no. 16 (April 21, 2009): 6650–55. https://doi.org/10.1073/pnas.0901083106.
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    • Shukla, Arun Kumar, Jihee Kim, Seungkirl Ahn, Kunhong Xiao, Wolfgang Liedtke, and Robert J. Lefkowitz. “[beta]-arrestin 1 mediates angiotensin II induced ubiquitination and down-regulation of TRPV4.” Faseb Journal 23 (April 1, 2009).
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    • Ahn, Seungkirl, Jihee Kim, Makoto R. Hara, Xiu-Rong Ren, and Robert J. Lefkowitz. “{beta}-Arrestin-2 Mediates Anti-apoptotic Signaling through Regulation of BAD Phosphorylation.” J Biol Chem 284, no. 13 (March 27, 2009): 8855–65. https://doi.org/10.1074/jbc.M808463200.
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    • DeWire, Scott M., Jihee Kim, Erin J. Whalen, Seungkirl Ahn, Minyong Chen, and Robert J. Lefkowitz. “Beta-arrestin-mediated signaling regulates protein synthesis.” J Biol Chem 283, no. 16 (April 18, 2008): 10611–20. https://doi.org/10.1074/jbc.M710515200.
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    • Wisler, James W., Scott M. DeWire, Erin J. Whalen, Jonathan D. Violin, Matthew T. Drake, Seungkirl Ahn, Sudha K. Shenoy, and Robert J. Lefkowitz. “A unique mechanism of beta-blocker action: carvedilol stimulates beta-arrestin signaling.” Proc Natl Acad Sci U S A 104, no. 42 (October 16, 2007): 16657–62. https://doi.org/10.1073/pnas.0707936104.
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    • Shenoy, Sudha K., Larry S. Barak, Kunhong Xiao, Seungkirl Ahn, Magali Berthouze, Arun K. Shukla, Louis M. Luttrell, and Robert J. Lefkowitz. “Ubiquitination of beta-arrestin links seven-transmembrane receptor endocytosis and ERK activation.” J Biol Chem 282, no. 40 (October 5, 2007): 29549–62. https://doi.org/10.1074/jbc.M700852200.
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    • DeWire, Scott M., Seungkirl Ahn, Robert J. Lefkowitz, and Sudha K. Shenoy. “Beta-arrestins and cell signaling.” Annu Rev Physiol 69 (2007): 483–510. https://doi.org/10.1146/annurev.physiol.69.022405.154749.
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    • Gesty-Palmer, Diane, Minyong Chen, Eric Reiter, Seungkirl Ahn, Christopher D. Nelson, Shuntai Wang, Allen E. Eckhardt, et al. “Distinct beta-arrestin- and G protein-dependent pathways for parathyroid hormone receptor-stimulated ERK1/2 activation.” J Biol Chem 281, no. 16 (April 21, 2006): 10856–64. https://doi.org/10.1074/jbc.M513380200.
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    • Kim, Jihee, Seungkirl Ahn, Xiu-Rong Ren, Erin J. Whalen, Eric Reiter, Huijun Wei, and Robert J. Lefkowitz. “Functional antagonism of different G protein-coupled receptor kinases for beta-arrestin-mediated angiotensin II receptor signaling.” Proc Natl Acad Sci U S A 102, no. 5 (February 1, 2005): 1442–47. https://doi.org/10.1073/pnas.0409532102.
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    • Ren, Xiu-Rong, Eric Reiter, Seungkirl Ahn, Jihee Kim, Wei Chen, and Robert J. Lefkowitz. “Different G protein-coupled receptor kinases govern G protein and beta-arrestin-mediated signaling of V2 vasopressin receptor.” Proc Natl Acad Sci U S A 102, no. 5 (February 1, 2005): 1448–53. https://doi.org/10.1073/pnas.0409534102.
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    • Wei, Huijun, Seungkirl Ahn, William G. Barnes, and Robert J. Lefkowitz. “Stable interaction between beta-arrestin 2 and angiotensin type 1A receptor is required for beta-arrestin 2-mediated activation of extracellular signal-regulated kinases 1 and 2.” J Biol Chem 279, no. 46 (November 12, 2004): 48255–61. https://doi.org/10.1074/jbc.M406205200.
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    • Ahn, Seungkirl, Sudha K. Shenoy, Huijun Wei, and Robert J. Lefkowitz. “Differential kinetic and spatial patterns of beta-arrestin and G protein-mediated ERK activation by the angiotensin II receptor.” J Biol Chem 279, no. 34 (August 20, 2004): 35518–25. https://doi.org/10.1074/jbc.M405878200.
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    • Ahn, Seungkirl, Huijun Wei, Tiffany Runyan Garrison, and Robert J. Lefkowitz. “Reciprocal regulation of angiotensin receptor-activated extracellular signal-regulated kinases by beta-arrestins 1 and 2.” J Biol Chem 279, no. 9 (February 27, 2004): 7807–11. https://doi.org/10.1074/jbc.C300443200.
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    • Wei, Huijun, Seungkirl Ahn, Sudha K. Shenoy, Sadashiva S. Karnik, László Hunyady, Louis M. Luttrell, and Robert J. Lefkowitz. “Independent beta-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2.” Proc Natl Acad Sci U S A 100, no. 19 (September 16, 2003): 10782–87. https://doi.org/10.1073/pnas.1834556100.
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    • Chen, Wei, Derk ten Berge, Jeff Brown, Seungkirl Ahn, Liaoyuan A. Hu, William E. Miller, Marc G. Caron, Larry S. Barak, Roel Nusse, and Robert J. Lefkowitz. “Dishevelled 2 recruits beta-arrestin 2 to mediate Wnt5A-stimulated endocytosis of Frizzled 4.” Science 301, no. 5638 (September 5, 2003): 1391–94. https://doi.org/10.1126/science.1082808.
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    • Kim, Jihee, Seungkirl Ahn, Rishu Guo, and Yehia Daaka. “Regulation of epidermal growth factor receptor internalization by G protein-coupled receptors.” Biochemistry 42, no. 10 (March 18, 2003): 2887–94. https://doi.org/10.1021/bi026942t.
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    • Ahn, Seungkirl, Christopher D. Nelson, Tiffany Runyan Garrison, William E. Miller, and Robert J. Lefkowitz. “Desensitization, internalization, and signaling functions of beta-arrestins demonstrated by RNA interference.” Proc Natl Acad Sci U S A 100, no. 4 (February 18, 2003): 1740–44. https://doi.org/10.1073/pnas.262789099.
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    • Ahn, Seungkirl, Jihee Kim, Carmen L. Lucaveche, Mary C. Reedy, Louis M. Luttrell, Robert J. Lefkowitz, and Yehia Daaka. “Src-dependent tyrosine phosphorylation regulates dynamin self-assembly and ligand-induced endocytosis of the epidermal growth factor receptor.” J Biol Chem 277, no. 29 (July 19, 2002): 26642–51. https://doi.org/10.1074/jbc.M201499200.
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    • Pierce, K. L., A. Tohgo, S. Ahn, M. E. Field, L. M. Luttrell, and R. J. Lefkowitz. “Epidermal growth factor (EGF) receptor-dependent ERK activation by G protein-coupled receptors: a co-culture system for identifying intermediates upstream and downstream of heparin-binding EGF shedding.” J Biol Chem 276, no. 25 (June 22, 2001): 23155–60. https://doi.org/10.1074/jbc.M101303200.
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    • Miller, W. E., S. Maudsley, S. Ahn, K. D. Khan, L. M. Luttrell, and R. J. Lefkowitz. “beta-arrestin1 interacts with the catalytic domain of the tyrosine kinase c-SRC. Role of beta-arrestin1-dependent targeting of c-SRC in receptor endocytosis.” J Biol Chem 275, no. 15 (April 14, 2000): 11312–19. https://doi.org/10.1074/jbc.275.15.11312.
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    • Maudsley, S., K. L. Pierce, A. M. Zamah, W. E. Miller, S. Ahn, Y. Daaka, R. J. Lefkowitz, and L. M. Luttrell. “The beta(2)-adrenergic receptor mediates extracellular signal-regulated kinase activation via assembly of a multi-receptor complex with the epidermal growth factor receptor.” J Biol Chem 275, no. 13 (March 31, 2000): 9572–80. https://doi.org/10.1074/jbc.275.13.9572.
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    • Ahn, S., S. Maudsley, L. M. Luttrell, R. J. Lefkowitz, and Y. Daaka. “Src-mediated tyrosine phosphorylation of dynamin is required for beta2-adrenergic receptor internalization and mitogen-activated protein kinase signaling.” J Biol Chem 274, no. 3 (January 15, 1999): 1185–88. https://doi.org/10.1074/jbc.274.3.1185.
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    • Stauffer, T. P., S. Ahn, and T. Meyer. “Receptor-induced transient reduction in plasma membrane PtdIns(4,5)P2 concentration monitored in living cells.” Curr Biol 8, no. 6 (March 12, 1998): 343–46. https://doi.org/10.1016/s0960-9822(98)70135-6.
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    • Daaka, Y., L. M. Luttrell, S. Ahn, G. J. Della Rocca, S. S. Ferguson, M. G. Caron, and R. J. Lefkowitz. “Essential role for G protein-coupled receptor endocytosis in the activation of mitogen-activated protein kinase.” J Biol Chem 273, no. 2 (January 9, 1998): 685–88. https://doi.org/10.1074/jbc.273.2.685.
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  • Conference Papers

    • Wang, Jialu, Ilhan Gokhan, Xinyu Xiong, Alem W. Kahsai, Haoran Jiang, Conrad T. Pfeiffer, William Tian, et al. “Abstract MP133: Development of β-arrestin-biased Positive Allosteric Modulators for the β ₁ Adrenergic Receptor.” In Circulation Research, Vol. 127. Ovid Technologies (Wolters Kluwer Health), 2020. https://doi.org/10.1161/res.127.suppl_1.mp133.
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    • Weiss, Dahlia R., SeungKirl Ahn, Maria F. Sassano, Andrew C. Kruse, Joel Karpiak, Bryan L. Roth, Brian K. Kobilka, Brian K. Shoichet, and Robert J. Lefkowitz. “G-protein coupled receptors in virtual screening: Functional fidelity and selectivity.” In Abstracts of Papers of the American Chemical Society, Vol. 245. AMER CHEMICAL SOC, 2013.
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