The Conformational Plasticity of Protein Kinases

Comparative Genomics of the Eukaryotes

Rubin, G. M., Yandell, M. D., Wortman, J. R., Gabor, G. L., Miklos, Nelson, C. R., Hariharan, I. K., Fortini, M. E., Li, P. W., Apweiler, R., et al. (2000) · Science · doi:10.1126/science.287.5461.2204 · Cited by 1,698

Atomic structure of the MAP kinase ERK2 at 2.3 A resolution

Zhang, F., Strand, A., Robbins, D., Cobb, M. H., & Goldsmith, E. J. (1994) · Nature · doi:10.1038/367704a0 · Cited by 592

EGFR Mutations in Lung Cancer: Correlation with Clinical Response to Gefitinib Therapy

Paez, J. G., Jänne, P. A., Lee, J. C., Tracy, S., Greulich, H., Gabriel, S., Herman, P., Kaye, F. J., Lindeman, N., Boggon, T. J., et al. (2004) · Science · doi:10.1126/science.1099314 · Cited by 9,368

Cell Signaling by Receptor Tyrosine Kinases

Lemmon, M. A., & Schlessinger, J. (2010) · Cell · doi:10.1016/j.cell.2010.06.011 · Cited by 7,929

EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib

Pao, W., Miller, V., Zakowski, M., Doherty, J., Politi, K., Sarkaria, I., Singh, B., Heelan, R., Rusch, V., Fulton, L., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405220101 · Cited by 4,338

DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation

Bakkenist, C. J., & Kastan, M. B. (2003) · Nature · doi:10.1038/nature01368 · Cited by 3,466

Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers

Shigematsu, H., Lin, L., Takahashi, T., Nomura, M., Suzuki, M., Wistuba, I. I., Fong, K. M., Lee, H., Toyooka, S., Shimizu, N., et al. (2005) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/dji055 · Cited by 2,377

HSP90 at the hub of protein homeostasis: emerging mechanistic insights

Taipale, M., Jarosz, D. F., & Lindquist, S. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2918 · Cited by 1,818

An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor

Zhang, X., Gureasko, J., Shen, K., Cole, P. A., & Kuriyan, J. (2006) · Cell · doi:10.1016/j.cell.2006.05.013 · Cited by 1,650

Epidermal growth factor receptor: Mechanisms of activation and signalling

Jorissen, R. (2003) · Experimental Cell Research · doi:10.1016/s0014-4827(02)00098-8 · Cited by 1,565

The Pseudokinase MLKL Mediates Necroptosis via a Molecular Switch Mechanism

Murphy, J. M., Czabotar, P. E., Hildebrand, J. M., Lucet, I. S., Zhang, J.-G., Alvarez-Diaz, S., Lewis, R., Lalaoui, N., Metcalf, D., Webb, A. I., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.06.018 · Cited by 1,220

Mechanisms of receptor tyrosine kinase activation in cancer

Du, Z., & Lovly, C. M. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0782-4 · Cited by 1,066

Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity

Anastassiadis, T., Deacon, S. W., Devarajan, K., Ma, H., & Peterson, J. R. (2011) · Nature Biotechnology · doi:10.1038/nbt.2017 · Cited by 919

Classification of small molecule protein kinase inhibitors based upon the structures of their drug-enzyme complexes

Roskoski, R. (2016) · Pharmacological Research · doi:10.1016/j.phrs.2015.10.021 · Cited by 886

Structure and regulation of Src family kinases

Boggon, T. J., & Eck, M. J. (2004) · Oncogene · doi:10.1038/sj.onc.1208081 · Cited by 712

Role of PINK1 Binding to the TOM Complex and Alternate Intracellular Membranes in Recruitment and Activation of the E3 Ligase Parkin

Lazarou, M., Jin, S. M., Kane, L. A., & Youle, R. J. (2012) · Developmental Cell · doi:10.1016/j.devcel.2011.12.014 · Cited by 670

Initiating Cellular Stress Responses

Bakkenist, C. J., & Kastan, M. B. (2004) · Cell · doi:10.1016/j.cell.2004.06.023 · Cited by 544

Regulation of the p300 HAT domain via a novel activation loop

Thompson, P. R., Wang, D., Wang, L., Fulco, M., Pediconi, N., Zhang, D., An, W., Ge, Q., Roeder, R. G., Wong, J., et al. (2004) · Nature Structural & Molecular Biology · doi:10.1038/nsmb740 · Cited by 423

Tethering: Fragment-Based Drug Discovery

Erlanson, D. A., Wells, J. A., & Braisted, A. C. (2004) · Annual Review of Biophysics and Biomolecular Structure · doi:10.1146/annurev.biophys.33.110502.140409 · Cited by 385

Defining a new nomenclature for the structures of active and inactive kinases

Modi, V., & Dunbrack, R. L. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1814279116 · Cited by 367

Molecular Mechanisms of HipA-Mediated Multidrug Tolerance and Its Neutralization by HipB

Schumacher, M. A., Piro, K. M., Xu, W., Hansen, S., Lewis, K., & Brennan, R. G. (2009) · Science · doi:10.1126/science.1163806 · Cited by 351

Signalling specificity of Ser/Thr protein kinases through docking-site-mediated interactions

BIONDI, R. M., & NEBREDA, A. R. (2003) · Biochemical Journal · doi:10.1042/bj20021641 · Cited by 334

Structural analysis of the catalytically inactive kinase domain of the human EGF receptor 3

Jura, N., Shan, Y., Cao, X., Shaw, D. E., & Kuriyan, J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912101106 · Cited by 338

Catalytic Control in the EGF Receptor and Its Connection to General Kinase Regulatory Mechanisms

Jura, N., Zhang, X., Endres, N. F., Seeliger, M. A., Schindler, T., & Kuriyan, J. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.03.004 · Cited by 310

A phosphoserine/threonine-binding pocket in AGC kinases and PDK1 mediates activation by hydrophobic motif phosphorylation

Frödin, M., Antal, T. L., Dümmler, B. A., Jensen, C. J., Deak, M., Gammeltoft, S., & Biondi, R. M. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf551 · Cited by 275

CASK Functions as a Mg2+-independent neurexin kinase

Mukherjee, K., Sharma, M., Urlaub, H., Bourenkov, G. P., Jahn, R., Südhof, T. C., & Wahl, M. C. (2008) · Cell · doi:10.1016/j.cell.2008.02.036 · Cited by 271

Blue light-induced autophosphorylation of phototropin is a primary step for signaling

Inoue, S.-I., Kinoshita, T., Matsumoto, M., Nakayama, K. I., Doi, M., & Shimazaki, K.-I. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709189105 · Cited by 269

Conformational states dynamically populated by a kinase determine its function

Xie, T., Saleh, T., Rossi, P., & Kalodimos, C. G. (2020) · Science · doi:10.1126/science.abc2754 · Cited by 266

Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530

Green, T. P., Fennell, M., Whittaker, R., Curwen, J., Jacobs, V., Allen, J., Logie, A., Hargreaves, J., Hickinson, D. M., Wilkinson, R. W., et al. (2009) · Molecular Oncology · doi:10.1016/j.molonc.2009.01.002 · Cited by 238

Saccharomyces cerevisiae Rad9 acts as a Mec1 adaptor to allow Rad53 activation

Sweeney, F. D., Yang, F., Chi, A., Shabanowitz, J., Hunt, D. F., & Durocher, D. (2005) · Current Biology · doi:10.1016/j.cub.2005.06.063 · Cited by 237

The structure and substrate specificity of human Cdk12/Cyclin K

Bösken, C. A., Farnung, L., Hintermair, C., Merzel Schachter, M., Vogel-Bachmayr, K., Blazek, D., Anand, K., Fisher, R. P., Eick, D., & Geyer, M. (2014) · Nature Communications · doi:10.1038/ncomms4505 · Cited by 191

Growth signalling pathways in Arabidopsis and the AGC protein kinases

Bögre, L. (2003) · Trends in Plant Science · doi:10.1016/s1360-1385(03)00188-2 · Cited by 190

Substrate and Docking Interactions in Serine/Threonine Protein Kinases

Goldsmith, E. J., Akella, R., Min, X., Zhou, T., & Humphreys, J. M. (2007) · Chemical Reviews · doi:10.1021/cr068221w · Cited by 143

The Role of Docking Interactions in Mediating Signaling Input, Output, and Discrimination in the Yeast MAPK Network

Reményi, A., Good, M. C., Bhattacharyya, R. P., & Lim, W. A. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.10.030 · Cited by 154

Structural and Energetic Mechanisms of Cooperative Autoinhibition and Activation of Vav1

Yu, B., Martins, I. R. S., Li, P., Amarasinghe, G. K., Umetani, J., Fernandez-Zapico, M. E., Billadeau, D. D., Machius, M., Tomchick, D. R., & Rosen, M. K. (2010) · Cell · doi:10.1016/j.cell.2009.12.033 · Cited by 156

Development of small-molecule tropomyosin receptor kinase (TRK) inhibitors for NTRK fusion cancers

Jiang, T., Wang, G., Liu, Y., Feng, L., Wang, M., Liu, J., Chen, Y., & Ouyang, L. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.05.004 · Cited by 157

Mechanistic insight into the dominant mode of the Parkinson's disease-associated G2019S LRRK2 mutation

Luzon-Toro, B., de la Torre, E. R., Delgado, A., Perez-Tur, J., & Hilfiker, S. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm151 · Cited by 122

AI-Based Protein Structure Prediction in Drug Discovery: Impacts and Challenges

Schauperl, M., & Denny, R. A. (2022) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.2c00026 · Cited by 122

Unraveling structural mechanisms of allosteric drug action

Nussinov, R., & Tsai, C.-J. (2014) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2014.03.006 · Cited by 119

Reciprocal Activation within a Kinase-Effector Complex Underlying Persistence of Structural LTP

Saneyoshi, T., Matsuno, H., Suzuki, A., Murakoshi, H., Hedrick, N. G., Agnello, E., O’Connell, R., Stratton, M. M., Yasuda, R., & Hayashi, Y. (2019) · Neuron · doi:10.1016/j.neuron.2019.04.012 · Cited by 119

The chaperones Hsp90 and Cdc37 mediate the maturation and stabilization of protein kinase C through a conserved PXXP motif in the C-terminal tail.

Gould, C. M., Kannan, N., Taylor, S. S., & Newton, A. C. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m808436200 · Cited by 113

Molecular mechanism of activation-triggered subunit exchange in Ca2+/calmodulin-dependent protein kinase II

Bhattacharyya, M., Stratton, M. M., Going, C. C., McSpadden, E. D., Huang, Y., Susa, A. C., Elleman, A., Cao, Y. M., Pappireddi, N., Burkhardt, P., et al. (2016) · eLife · doi:10.7554/elife.13405 · Cited by 112

Structure of ERK2 bound to PEA-15 reveals a mechanism for rapid release of activated MAPK

Mace, P. D., Wallez, Y., Egger, M. F., Dobaczewska, M. K., Robinson, H., Pasquale, E. B., & Riedl, S. J. (2013) · Nature Communications · doi:10.1038/ncomms2687 · Cited by 97

Structural Insights into the Regulation of Ca2+/Calmodulin-Dependent Protein Kinase II (CaMKII)

Bhattacharyya, M., Karandur, D., & Kuriyan, J. (2020) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a035147 · Cited by 95

Autophosphorylation Within the Atg1 Activation Loop Is Required for Both Kinase Activity and the Induction of Autophagy in Saccharomyces cerevisiae

Yeh, Y.-Y., Wrasman, K., & Herman, P. K. (2010) · Genetics · doi:10.1534/genetics.110.116566 · Cited by 94

Towards simple kinetic models of functional dynamics for a kinase subfamily

Sultan, M. M., Kiss, G., & Pande, V. S. (2018) · Nature Chemistry · doi:10.1038/s41557-018-0077-9 · Cited by 68

Deep learning–guided design of dynamic proteins

Guo, A. B., Akpinaroglu, D., Stephens, C. A., Grabe, M., Smith, C. A., Kelly, M. J. S., & Kortemme, T. (2025) · Science · doi:10.1126/science.adr7094 · Cited by 67

Catalytically Active MAP KAP Kinase 2 Structures in Complex with Staurosporine and ADP Reveal Differences with the Autoinhibited Enzyme

Underwood, K. W., Parris, K. D., Federico, E., Mosyak, L., Czerwinski, R. M., Shane, T., Taylor, M., Svenson, K., Liu, Y., Hsiao, C.-L., et al. (2003) · Structure · doi:10.1016/s0969-2126(03)00092-3 · Cited by 62

Flexible linkers in CaMKII control the balance between activating and inhibitory autophosphorylation

Bhattacharyya, M., Lee, Y. K., Muratcioglu, S., Qiu, B., Nyayapati, P., Schulman, H., Groves, J. T., & Kuriyan, J. (2020) · eLife · doi:10.7554/elife.53670 · Cited by 58

The use of structural biology in Janus kinase targeted drug discovery

L. Alicea-Velazquez, N., & J. Boggon, T. (2011) · Current Drug Targets · doi:10.2174/138945011794751528 · Cited by 53

Structural basis for activation of the autoinhibitory C-terminal kinase domain of p90 RSK2

Malakhova, M., Tereshko, V., Lee, S.-Y., Yao, K., Cho, Y.-Y., Bode, A., & Dong, Z. (2008) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1347 · Cited by 48

Remote loop evolution reveals a complex biological function for chitinase enzymes beyond the active site

(2024) · doi:10.1038/s41467-024-47588-8 · Cited by 30

Conserved regulatory motifs in the juxtamembrane domain and kinase N-lobe revealed through deep mutational scanning of the MET receptor tyrosine kinase domain

Estevam, G. O., Linossi, E. M., Macdonald, C. B., Espinoza, C. A., Michaud, J. M., Coyote-Maestas, W., Collisson, E. A., Jura, N., & Fraser, J. S. (2024) · eLife · doi:10.7554/elife.91619 · Cited by 22

An ire1-phk1 chimera reveals a dispensable role of autokinase activity in endoplasmic reticulum stress response

Mannan, M. A.-U., Shadrick, W. R., Biener, G., Shin, B.-S., Anshu, A., Raicu, V., Frick, D. N., & Dey, M. (2013) · Journal of Molecular Biology · doi:10.1016/j.jmb.2013.02.036 · Cited by 18

Dynamic Protein Allosteric Regulation and Disease

Nussinov, R., Tsai, C.-J., & Jang, H. (2019) · Advances in Experimental Medicine and Biology · doi:10.1007/978-981-13-8719-7_2 · Cited by 18

NMR Spectroscopic Investigations of the Activated p38α Mitogen‐Activated Protein Kinase

Nielsen, G., & Schwalbe, H. (2011) · ChemBioChem · doi:10.1002/cbic.201100527 · Cited by 15

Validation of an Allosteric Binding Site of Src Kinase Identified by Unbiased Ligand Binding Simulations

Mingione, V. R., Foda, Z. H., Paung, Y., Philipose, H., Rangwala, A. M., Shan, Y., & Seeliger, M. A. (2022) · Journal of Molecular Biology · doi:10.1016/j.jmb.2022.167628 · Cited by 13

Therapeutic Targeting the Allosteric Cysteinome of RAS and Kinase Families

Li, L., Meyer, C., Zhou, Z.-W., Elmezayen, A., & Westover, K. (2022) · Journal of Molecular Biology · doi:10.1016/j.jmb.2022.167626 · Cited by 14

Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain

Howard, P. G., Zou, P., Zhang, Y., Huang, F., Tesic, V., Wu, C. Y.-C., & Lee, R. H.-C. (2024) · Experimental Neurology · doi:10.1016/j.expneurol.2024.114973 · Cited by 13

Dark kinase annotation, mining, and visualization using the Protein Kinase Ontology

Soleymani, S., Gravel, N., Huang, L.-C., Yeung, W., Bozorgi, E., Bendzunas, N. G., Kochut, K. J., & Kannan, N. (2023) · PeerJ · doi:10.7717/peerj.16087 · Cited by 13

Pyrazolo[1,5-a]pyrimidine as a Prominent Framework for Tropomyosin Receptor Kinase (Trk) Inhibitors—Synthetic Strategies and SAR Insights

Mahajan, A. T., Shivani, Datusalia, A. K., Coluccini, C., Coghi, P., & Chaudhary, S. (2024) · Molecules · doi:10.3390/molecules29153560 · Cited by 12

Activation loop phosphorylation tunes conformational dynamics underlying Pyk2 tyrosine kinase activation

Palhano Zanela, T. M., Woudenberg, A., Romero Bello, K. G., & Underbakke, E. S. (2023) · Structure · doi:10.1016/j.str.2023.02.003 · Cited by 12

Deep learning guided design of dynamic proteins

Guo, A. B., Akpinaroglu, D., Kelly, M. J. S., & Kortemme, T. (2024) · doi:10.1101/2024.07.17.603962 · Cited by 9

Structure and regulation of full-length human leucine-rich repeat kinase 1

Metcalfe, R. D., Martinez Fiesco, J. A., Bonet-Ponce, L., Kluss, J. H., Cookson, M. R., & Zhang, P. (2023) · Nature Communications · doi:10.1038/s41467-023-40532-2 · Cited by 8

Molecular requirements for PLK1 activation by T-loop phosphorylation

(2026) · doi:10.1038/s44318-025-00681-0 · Cited by 8

Structural basis for kinase inhibition in the tripartite E. coli HipBST toxin-antitoxin system

Bærentsen, R. L., Nielsen, S. V., Skjerning, R. B., Lyngsø, J., Bisiak, F., Pedersen, J. S., Gerdes, K., Sørensen, M. A., & Brodersen, D. E. (2023) · doi:10.7554/elife.90400.2 · Cited by 1

Narrow funnel-like interaction energy distribution is an indicator of specific protein interaction partner

Choi, J. (2023) · iScience · doi:10.1016/j.isci.2023.106911 · Cited by 1