The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
GTP-Dependent K-Ras Dimerization
Open accessAbstract
Ras proteins recruit and activate effectors, including Raf, that transmit receptor-initiated signals. Monomeric Ras can bind Raf; however, activation of Raf requires its dimerization. It has been suspected that dimeric Ras may promote dimerization and activation of Raf. Here, we show that the GTP-bound catalytic domain of K-Ras4B, a highly oncogenic splice variant of the K-Ras isoform, forms stable homodimers. We observe two major dimer interfaces. The first, highly populated β-sheet dimer interface is at the Switch I and effector binding regions, overlapping the binding surfaces of Raf, PI3K, RalGDS, and additional effectors. This interface has to be inhibitory to such effectors. The second, helical interface also overlaps the binding sites of some effectors. This interface may promote activation of Raf. Our data reveal how Ras self-association can regulate effector binding and activity, and suggest that disruption of the helical dimer interface by drugs may abate Raf signaling in cancer.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The KRAS dimerization is a GTP-dependent process [67].”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Discovery and saturation analysis of cancer genes across 21 tumour types
Lawrence, M. S., Stojanov, P., Mermel, C. H., Robinson, J. T., Garraway, L. A., Golub, T. R., Meyerson, M., Gabriel, S. B., Lander, E. S., & Getz, G. (2014) · Nature · doi:10.1038/nature12912 · Cited by 3,096 · cited 1×
“K-Ras, which is frequently mutated in human cancer (Lawrence et al., 2014), is the most potent activator of Raf among Ras isoforms (Prior et al., 2012).”
BackgroundA Comprehensive Survey of Ras Mutations in Cancer
Prior, I. A., Lewis, P. D., & Mattos, C. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-2612 · Cited by 2,063 · cited 2×
“K-Ras, which is frequently mutated in human cancer (Lawrence et al., 2014), is the most potent activator of Raf among Ras isoforms (Prior et al., 2012).”
BackgroundRas oncogenes: split personalities
Karnoub, A. E., & Weinberg, R. A. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2438 · Cited by 1,467
Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions
Kölch, W. (2000) · Biochemical Journal · doi:10.1042/bj3510289 · Cited by 1,443
Hancock, J. F., Paterson, H., & Marshall, C. J. (1990) · Cell · doi:10.1016/0092-8674(90)90294-o · Cited by 1,042
Molecular Interaction Studies Using Microscale Thermophoresis
Jerabek‐Willemsen, M., Wienken, C. J., Braun, D., Baaske, P., & Duhr, S. (2011) · Assay and Drug Development Technologies · doi:10.1089/adt.2011.0380 · Cited by 820
Stephen, A. G., Esposito, D., Bagni, R. K., & McCormick, F. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.02.017 · Cited by 795
RAS Interaction with PI3K: More Than Just Another Effector Pathway
Castellano, E., & Downward, J. (2011) · Genes & Cancer · doi:10.1177/1947601911408079 · Cited by 762
Principles of Protein−Protein Interactions: What are the Preferred Ways For Proteins To Interact?
Keskin, O., Gursoy, A., Ma, B., & Nussinov, R. (2008) · Chemical Reviews · doi:10.1021/cr040409x · Cited by 697
Self-citationThe RCSB Protein Data Bank: views of structural biology for basic and applied research and education
Rose, P. W., Prlić, A., Bi, C., Bluhm, W. F., Christie, C. H., Dutta, S., Green, R. K., Goodsell, D. S., Westbrook, J., Woo, J., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku1214 · Cited by 519
Cited by
Sorted by citations
RAS-targeted therapies: is the undruggable drugged?
Moore, A. R., Rosenberg, S. C., McCormick, F., & Malek, S. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0068-6 · Cited by 1,103
Molecular Dynamics Simulations in Drug Discovery and Pharmaceutical Development
Salo‐Ahen, O. M. H., Alanko, I., Bhadane, R. N., Bonvin, A. M. J. J., Honorato, R. V., Hossain, S., Juffer, A. H., Kabedev, A., Lahtela-Kakkonen, M. K., Larsen, A. S., et al. (2020) · Processes · doi:10.3390/pr9010071 · Cited by 732
Direct small-molecule inhibitors of KRAS: from structural insights to mechanism-based design
Ostrem, J. M. L., & Shokat, K. M. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.139 · Cited by 641
Ras Conformational Ensembles, Allostery, and Signaling
Lu, S., Jang, H., Muratcioglu, S., Gursoy, A., Keskin, O., Nussinov, R., & Zhang, J. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00542 · Cited by 355
Self-citationInhibition of RAS function through targeting an allosteric regulatory site
Spencer-Smith, R., Koide, A., Zhou, Y., Eguchi, R. R., Sha, F., Gajwani, P., Santana, D., Gupta, A., Jacobs, M., Herrero-Garcia, E., et al. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2231 · Cited by 283
Lipid-Sorting Specificity Encoded in K-Ras Membrane Anchor Regulates Signal Output
Zhou, Y., Prakash, P., Hong, L., Cho, K., Gorfe, A. A., & Hancock, J. F. (2016) · Cell · doi:10.1016/j.cell.2016.11.059 · Cited by 292
The current understanding of KRAS protein structure and dynamics
Pantsar, T. (2019) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2019.12.004 · Cited by 304
KRAS Dimerization Impacts MEK Inhibitor Sensitivity and Oncogenic Activity of Mutant KRAS
Ambrogio, C., Köhler, J., Zhou, Z.-W., Wang, H., Paranal, R., Li, J., Capelletti, M., Caffarra, C., Li, S., Lv, Q., et al. (2018) · Cell · doi:10.1016/j.cell.2017.12.020 · Cited by 270
The Structural Basis of Oncogenic Mutations G12, G13 and Q61 in Small GTPase K-Ras4B
Lu, S., Jang, H., Nussinov, R., & Zhang, J. (2016) · Scientific Reports · doi:10.1038/srep21949 · Cited by 219
Self-citationExtracellular-Regulated Kinases: Signaling From Ras to ERK Substrates to Control Biological Outcomes
Eblen, S. T. (2018) · Advances in cancer research · doi:10.1016/bs.acr.2018.02.004 · Cited by 217
Drugging Ras GTPase: a comprehensive mechanistic and signaling structural view
Lu, S., Jang, H., Gu, S., Zhang, J., & Nussinov, R. (2016) · Chemical Society Reviews · doi:10.1039/c5cs00911a · Cited by 188
Self-citationPrakash, P., Zhou, Y., Hong, L., Hancock, J. F., & Gorfe, A. A. (2016) · Biophysical Journal · doi:10.1016/j.bpj.2016.01.019 · Cited by 135
Deconstruction of the Ras switching cycle through saturation mutagenesis
Bandaru, P., Shah, N. H., Bhattacharyya, M., Barton, J. P., Kondo, Y., Cofsky, J. C., Gee, C. L., Chakraborty, A. K., Kortemme, T., Ranganathan, R., et al. (2017) · eLife · doi:10.7554/elife.27810 · Cited by 117
Nussinov, R., Jang, H., Tsai, C., & Cheng, F. (2019) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1006658 · Cited by 134
Self-citationOncogenic Ras Isoforms Signaling Specificity at the Membrane
Nussinov, R., Tsai, C., & Jang, H. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-2727 · Cited by 124
Self-citationNavigating the ERK1/2 MAPK Cascade
Martín-Vega, A., & Cobb, M. H. (2023) · Biomolecules · doi:10.3390/biom13101555 · Cited by 127
Therapeutic targeting of RAS: New hope for drugging the “undruggable”
Khan, I., Rhett, J. M., & O’Bryan, J. P. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2019.118570 · Cited by 111
Genetic Heterogeneity of BRAF Fusion Kinases in Melanoma Affects Drug Responses
Botton, T., Talevich, E., Mishra, V. K., Zhang, T., Shain, A. H., Berquet, C., Gagnon, A., Judson, R. L., Ballotti, R., Ribas, A., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.09.009 · Cited by 113
Falconer, R. (2016) · Journal of Molecular Recognition · doi:10.1002/jmr.2550 · Cited by 94
KRAS-specific inhibition using a DARPin binding to a site in the allosteric lobe
Bery, N., Legg, S., Debreczeni, J., Breed, J., Embrey, K., Stubbs, C., Kolasinska-Zwierz, P., Barrett, N., Marwood, R., Watson, J., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10419-2 · Cited by 97
Membrane-associated Ras dimers are isoform-specific: K-Ras dimers differ from H-Ras dimers
Jang, H., Muratcioğlu, S., Gürsoy, A., Keskin, Ö., & Nussinov, R. (2016) · Biochemical Journal · doi:10.1042/bcj20160031 · Cited by 91
Self-citationPrakash, P., Sayyed–Ahmad, A., Cho, K.-J., Dolino, D. M., Chen, W., Li, H., Grant, B. J., Hancock, J. F., & Gorfe, A. A. (2017) · Scientific Reports · doi:10.1038/srep40109 · Cited by 93
Ingólfsson, H. I., Neale, C., Carpenter, T. S., Shrestha, R., López, C. A., Tran, T. H., Oppelstrup, T., Bhatia, H., Stanton, L. G., Zhang, X., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2113297119 · Cited by 96
A New View of Ras Isoforms in Cancers
Nussinov, R., Tsai, C., Chakrabarti, M., & Jang, H. (2015) · Cancer Research · doi:10.1158/0008-5472.can-15-1536 · Cited by 92
Self-citationRas and the Plasma Membrane: A Complicated RelationshipPreprint
Zhou, Y., Prakash, P., Gorfe, A. A., & Hancock, J. F. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a031831 · Cited by 87
The Ras switch in structural and historical perspective
Gasper, R., & Wittinghofer, F. (2019) · Biological Chemistry · doi:10.1515/hsz-2019-0330 · Cited by 92
Pantsar, T., Rissanen, S., Dauch, D., Laitinen, T., Vattulainen, I., & Poso, A. (2018) · PLOS Computational Biology · doi:10.1371/journal.pcbi.1006458 · Cited by 85
Lu, S., Banerjee, A., Jang, H., Zhang, J., Gaponenko, V., & Nussinov, R. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.664755 · Cited by 86
Self-citationMolecular recognition of RAS/RAF complex at the membrane: Role of RAF cysteine-rich domain
Travers, T. S., López, C. A., Van, Q. N., Neale, C., Tonelli, M., Stephen, A. G., & Gnanakaran, S. (2018) · Scientific Reports · doi:10.1038/s41598-018-26832-4 · Cited by 82
Sarkar‐Banerjee, S., Sayyed–Ahmad, A., Prakash, P., Cho, K., Waxham, M. N., Hancock, J. F., & Gorfe, A. A. (2017) · Journal of the American Chemical Society · doi:10.1021/jacs.7b06292 · Cited by 78
Li, S., Jang, H., Zhang, J., & Nussinov, R. (2018) · Structure · doi:10.1016/j.str.2018.01.011 · Cited by 76
Self-citationLee, K., Fang, Z., Enomoto, M., Gasmi-Seabrook, G. M. C., Zheng, L., Koide, S., Ikura, M., & Marshall, C. B. (2020) · Angewandte Chemie International Edition · doi:10.1002/anie.202001758 · Cited by 78
Targeting the MAPK Pathway in RAS Mutant CancersPreprint
Hymowitz, S. G., & Malek, S. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a031492 · Cited by 78
The Key Role of Calmodulin in KRAS-Driven Adenocarcinomas
Nussinov, R., Muratcioğlu, S., Tsai, C., Jang, H., Gürsoy, A., & Keskin, Ö. (2015) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-15-0165 · Cited by 78
Self-citationThe higher level of complexity of K‐Ras4B activation at the membrane
Jang, H., Banerjee, A., Chavan, T., Lu, S., Zhang, J., Gaponenko, V., & Nussinov, R. (2015) · The FASEB Journal · doi:10.1096/fj.15-279091 · Cited by 75
Self-citationInhibitors of Ras–SOS Interactions
Lu, S., Jang, H., Zhang, J., & Nussinov, R. (2016) · ChemMedChem · doi:10.1002/cmdc.201500481 · Cited by 72
Self-citationK-Ras4B Remains Monomeric on Membranes over a Wide Range of Surface Densities and Lipid Compositions
Chung, J. K., Lee, Y. K., Denson, J.-P., Gillette, W., Alvarez, S. A., Stephen, A. G., & Groves, J. T. (2018) · Biophysical Journal · doi:10.1016/j.bpj.2017.10.042 · Cited by 72
The RAS-Effector Interface: Isoform-Specific Differences in the Effector Binding Regions
Nakhaeizadeh, H., Amin, E., Nakhaei‐Rad, S., Dvorský, R., & Ahmadian, M. R. (2016) · PLoS ONE · doi:10.1371/journal.pone.0167145 · Cited by 71
Li, Z., Prakash, P., & Buck, M. (2018) · ACS Central Science · doi:10.1021/acscentsci.7b00593 · Cited by 71
A structural model of a Ras–Raf signalosome
Mysore, V. P., Zhou, Z.-W., Ambrogio, C., Li, L., Kapp, J. N., Lu, C., Wang, Q., Tucker, M. R., Okoro, J. J., Nagy‐Davidescu, G., et al. (2021) · Nature Structural & Molecular Biology · doi:10.1038/s41594-021-00667-6 · Cited by 69
Cookis, T., & Mattos, C. (2021) · Biomolecules · doi:10.3390/biom11070996 · Cited by 62
Allostery: Allosteric Cancer Drivers and Innovative Allosteric Drugs
Nussinov, R., Zhang, M., Maloney, R., Liu, Y., Tsai, C.-J., & Jang, H. (2022) · Journal of Molecular Biology · doi:10.1016/j.jmb.2022.167569 · Cited by 66
Self-citationPathogen mimicry of host protein-protein interfaces modulates immunity
Guven‐Maiorov, E., Tsai, C., & Nussinov, R. (2016) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2016.06.004 · Cited by 72
Self-citationDIRAS3 (ARHI) Blocks RAS/MAPK Signaling by Binding Directly to RAS and Disrupting RAS Clusters
Sutton, M. N., Lü, Z., Li, Y.-C., Zhou, Y., Huang, T., Reger, A. S., Hurwitz, A. M., Palzkill, T. G., Logsdon, C. D., Liang, X., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.11.045 · Cited by 68
Cao, S., Chung, S., Kim, S., Li, Z., Manor, D., & Buck, M. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.004021 · Cited by 63
The structure of neurofibromin isoform 2 reveals different functional states
Naschberger, A., Baradaran, R., Rupp, B., & Carroni, M. (2021) · Nature · doi:10.1038/s41586-021-04024-x · Cited by 62
The quaternary assembly of KRas4B with Raf-1 at the membrane
Jang, H., Zhang, M., & Nussinov, R. (2020) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2020.03.018 · Cited by 57
Self-citationThe membrane surface as a platform that organizes cellular and biochemical processes
Leonard, T. A., Loose, M., & Martens, S. (2023) · Developmental Cell · doi:10.1016/j.devcel.2023.06.001 · Cited by 64
ProtCID: a data resource for structural information on protein interactions
Xu, Q., & Dunbrack, R. L. (2020) · Nature Communications · doi:10.1038/s41467-020-14301-4 · Cited by 61
KRAS: Biology, Inhibition, and Mechanisms of Inhibitor Resistance
Ash, L. J., Busia-Bourdain, O., Okpattah, D., Kamel, A., Liberchuk, A., & Wolfe, A. L. (2024) · Current Oncology · doi:10.3390/curroncol31040150 · Cited by 68
“Onco-genic KRAS has been identified as a key player in inducing significant metabolic changes in cells and can drive alterations in various metabolic pathways, including glycolysis, glu-Curr taminolysis, and micropinocytosis [24].”
BackgroundLamprakis, C., Andreadelis, I., Manchester, J. I., Velez‐Vega, C., Duca, J. S., & Cournia, Z. (2021) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.0c00507 · Cited by 59
Uncovering a membrane-distal conformation of KRAS available to recruit RAF to the plasma membrane
Van, Q. N., López, C. A., Tonelli, M., Taylor, T. E., Niu, B., Stanley, C. B., Bhowmik, D., Tran, T. H., Frank, P. H., Messing, S. A. J., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2006504117 · Cited by 58
Zhou, Z.-W., Ambrogio, C., Bera, A. K., Li, Q., Li, X.-X., Li, L., Son, J., Gondi, S., Li, J., Campbell, E., et al. (2020) · Cancer Research · doi:10.1158/0008-5472.can-20-0448 · Cited by 60
Intrinsic protein disorder in oncogenic KRAS signaling
Nussinov, R., Jang, H., Tsai, C., Liao, T.-J., Li, S., Fushman, D., & Zhang, J. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2564-3 · Cited by 58
Self-citationRaf promotes dimerization of the Ras G-domain with increased allosteric connections
Packer, M. R., Parker, J. A., Chung, J. K., Li, Z., Lee, Y. K., Cookis, T., Guterres, H., Alvarez, S. A., Hossain, M. A., Donnelly, D. P., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2015648118 · Cited by 55
Simanshu, D. K., Philips, M. R., & Hancock, J. F. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.03.008 · Cited by 54
Ingólfsson, H. I., Bhatia, H., Aydin, F., Oppelstrup, T., López, C. A., Stanton, L. G., Carpenter, T. S., Wong, S., Natale, F. D., Zhang, X., et al. (2023) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.2c01018 · Cited by 60
KRAS: A Druggable Target in Colon Cancer Patients
Negri, F., Bottarelli, L., de’Angelis, G. L., & Gnetti, L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084120 · Cited by 57
40 Years of RAS—A Historic Overview
Fernández‐Medarde, A., Rivas, J. D. L., & Santos, E. (2021) · Genes · doi:10.3390/genes12050681 · Cited by 57
Chakrabarti, M., Jang, H., & Nussinov, R. (2016) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.5b11110 · Cited by 52
Self-citationBildik, G., Liang, X., Sutton, M. N., Bast, R. C., & Lü, Z. (2021) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-21-0331 · Cited by 55
Šolman, M., Ligabue, A., Blaževitš, O., Jaiswal, A., Zhou, Y., Hong, L., Lectez, B. L. P., Kopra, K., Guzmán, C., Härmä, H., et al. (2015) · eLife · doi:10.7554/elife.08905 · Cited by 48
Sayyed–Ahmad, A., Cho, K., Hancock, J. F., & Gorfe, A. A. (2016) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.6b02403 · Cited by 50
Structural impact of GTP binding on downstream KRAS signaling
Menyhárd, D. K., Pálfy, G., Orgován, Z., Vida, I., Keserű, G. M., & Perczel, A. (2020) · Chemical Science · doi:10.1039/d0sc03441j · Cited by 50
Ras Dimer Formation as a New Signaling Mechanism and Potential Cancer Therapeutic Target
Chen, M., Peters, A., Huang, T., & Nan, X. (2015) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/1389557515666151001152212 · Cited by 49
Membrane orientation dynamics of lipid-modified small GTPases
Prakash, P., & Gorfe, A. A. (2016) · Small GTPases · doi:10.1080/21541248.2016.1211067 · Cited by 48
Mechanisms of Ras Membrane Organization and Signaling: Ras Rocks Again
Abankwa, D., & Gorfe, A. A. (2020) · Biomolecules · doi:10.3390/biom10111522 · Cited by 46
Intrinsically disordered proteins: Ensembles at the limits of Anfinsen's dogma
Kulkarni, P., Leite, V. B. P., Roy, S., Bhattacharyya, S., Mohanty, A. R., Achuthan, S., Singh, D., Appadurai, R., Govindan Rangarajan, C., Weninger, K., et al. (2022) · Biophysics Reviews · doi:10.1063/5.0080512 · Cited by 49
Cammarata, M. B., Schardon, C. L., Mehaffey, M. R., Rosenberg, J. A., Singleton, J. P., Fast, W. L., & Brodbelt, J. S. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.6b04474 · Cited by 45
Vatansever, S., Gumus, Z. H., & Erman, B. (2016) · Scientific Reports · doi:10.1038/srep37012 · Cited by 45
KRAS(G12C)–AMG 510 interaction dynamics revealed by all-atom molecular dynamics simulations
Pantsar, T. (2020) · Scientific Reports · doi:10.1038/s41598-020-68950-y · Cited by 45
Plasma membrane regulates Ras signaling networks
Chavan, T., Muratcioğlu, S., Marszalek, R. J., Jang, H., Keskin, Ö., Gürsoy, A., Nussinov, R., & Gaponenko, V. (2015) · Cellular Logistics · doi:10.1080/21592799.2015.1136374 · Cited by 43
Self-citationJang, H., Banerjee, A., Chavan, T., Gaponenko, V., & Nussinov, R. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.785063 · Cited by 43
Self-citationBanerjee, A., Jang, H., Nussinov, R., & Gaponenko, V. (2015) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2015.11.010 · Cited by 42
Self-citationNussinov, R., Tsai, C., Muratcioğlu, S., Jang, H., Gürsoy, A., & Keskin, Ö. (2015) · Expert Review of Proteomics · doi:10.1586/14789450.2015.1100079 · Cited by 42
Self-citationCovalent Ras Dimerization on Membrane Surfaces through Photosensitized Oxidation
Chung, J. K., Lee, Y. K., Lam, H. Y. M., & Groves, J. T. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.5b12648 · Cited by 38
Killoran, R. C., & Smith, M. J. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.008653 · Cited by 41
Lee, K.-Y., Enomoto, M., Gebregiworgis, T., Gasmi-Seabrook, G. M. C., Ikura, M., & Marshall, C. B. (2021) · Chemical Science · doi:10.1039/d1sc03484g · Cited by 41
New structural and functional insight into the regulation of Ras
Kano, Y., Cook, J. D., Lee, J. E., & Ohh, M. (2016) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2016.06.006 · Cited by 38
KRAS: A Promising Therapeutic Target for Cancer Treatment
Wu, H.-Z., Xiao, J., Xiao, S., & Cheng, Y. (2019) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026619666190905164144 · Cited by 41
Insights into K-Ras 4B regulation by post-translational lysine acetylation
Knyphausen, P., Lang, F., Baldus, L., Extra, A., & Lammers, M. (2016) · Biological Chemistry · doi:10.1515/hsz-2016-0118 · Cited by 39
Erazo‐Oliveras, A., Fuentes, N. R., Wright, R. C., & Chapkin, R. S. (2018) · Cancer and Metastasis Reviews · doi:10.1007/s10555-018-9733-1 · Cited by 38
Approaches to inhibiting oncogenic K-Ras
Gorfe, A. A., & Cho, K. (2019) · Small GTPases · doi:10.1080/21541248.2019.1655883 · Cited by 36
Shi, H. M., Ju, Q., Mao, Y., Wang, Y., Ding, J., Liu, X., Tang, X., & Sun, C. (2021) · Advanced Science · doi:10.1002/advs.202001575 · Cited by 35
Tang, R., Shuldiner, E. G., Kelly, M. R., Murray, C. W., Hebert, J. D., Andrejka, L., Tsai, M. K., Hughes, N. W., Parker, M. I., Cai, H., et al. (2023) · Nature Cell Biology · doi:10.1038/s41556-022-01049-w · Cited by 38
RAS Nanoclusters: Dynamic Signaling Platforms Amenable to Therapeutic Intervention
Van, Q. N., Prakash, P., Shrestha, R., Balius, T. E., Turbyville, T. J., & Stephen, A. G. (2021) · Biomolecules · doi:10.3390/biom11030377 · Cited by 34
Dysregulation of cellular membrane homeostasis as a crucial modulator of cancer risk
Erazo‐Oliveras, A., Muñoz‐Vega, M., Salinas, M. L., Wang, X., & Chapkin, R. S. (2022) · FEBS Journal · doi:10.1111/febs.16665 · Cited by 38
Nussinov, R. (2025) · Journal of Molecular Biology · doi:10.1016/j.jmb.2025.169044 · Cited by 34
Self-citationRASSF5: An MST activator and tumor suppressor in vivo but opposite in vitro
Liao, T.-J., Tsai, C., Jang, H., Fushman, D., & Nussinov, R. (2016) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2016.09.001 · Cited by 30
Self-citationMehaffey, M. R., Schardon, C. L., Novelli, E. T., Cammarata, M. B., Webb, L. J., Fast, W. L., & Brodbelt, J. S. (2019) · Chemical Science · doi:10.1039/c9sc01032g · Cited by 31
K-Ras4B/calmodulin/PI3Kα: A promising new adenocarcinoma-specific drug target?
Nussinov, R., Muratcioğlu, S., Tsai, C., Jang, H., Gürsoy, A., & Keskin, Ö. (2015) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2016.1135131 · Cited by 30
Self-citationNi, D., Song, K., Zhang, J., & Lu, S. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18112249 · Cited by 30
Signaling pathways downstream to receptor tyrosine kinases: targets for cancer treatment
Cordover, E., & Minden, A. (2020) · Journal of Cancer Metastasis and Treatment · doi:10.20517/2394-4722.2020.101 · Cited by 31
PDEδ Binding to Ras Isoforms Provides a Route to Proper Membrane Localization
Muratcioğlu, S., Jang, H., Gürsoy, A., Keskin, Ö., & Nussinov, R. (2017) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.7b03035 · Cited by 30
Self-citationInhibition of Nonfunctional Ras
Nussinov, R., Jang, H., Gürsoy, A., Keskin, Ö., & Gaponenko, V. (2021) · Cell chemical biology · doi:10.1016/j.chembiol.2020.12.012 · Cited by 29
Self-citationThe renewed battle against RAS-mutant cancers
Zhang, F., & Cheong, J. K. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2155-8 · Cited by 30
Allosteric activation of RAF in the MAPK signaling pathway
Tsai, C., & Nussinov, R. (2018) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2018.07.007 · Cited by 27
Self-citationBiology, pathology, and therapeutic targeting of RAS
Rhett, J. M., Khan, I., & O’Bryan, J. P. (2020) · Advances in cancer research · doi:10.1016/bs.acr.2020.05.002 · Cited by 29
Sayyed–Ahmad, A., & Gorfe, A. A. (2017) · Journal of Chemical Theory and Computation · doi:10.1021/acs.jctc.7b00130 · Cited by 28
Molecular dynamics simulations for the structure-based drug design: targeting small-GTPases proteins
Parise, A., Cresca, S., & Magistrato, A. (2024) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2024.2387856 · Cited by 27
Metadata
- Authors
- Muratcioglu, S., Chavan, T. S., Freed, B. C., Jang, H., Khavrutskii, L., Freed, R. N., Dyba, M. A., Stefanisko, K., Tarasov, S. G., Gursoy, A., Keskin, O., Tarasova, N. I., Gaponenko, V., & Nussinov, R.
- Affiliations
- University of Illinois Chicago (US)
- National Cancer Institute (US)
- Frederick National Laboratory for Cancer Research (US)
- Tel Aviv University (IL)
- Corresponding author
- Gaponenko, Vadim
- Nussinov, Ruth
- ORCID
- Venue
- Structure
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 23
- Issue
- 7
- Pages
- 1325-1335
- ISSN
- 0969-2126 (ISSN-L)
- PMC
- PMC4497850
- OpenAlex
- W1535997186
- Cited by
- 202
- References
- 52
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 12 · 2023: 15 · 2022: 17 · 2021: 23 · 2020: 27 · 2019: 21 · 2018: 22 · 2017: 15 · 2016: 30 · 2015: 12
- FWCI
- 10.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Structure (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (HHSN261200800001C)
- National Heart, Lung, and Blood Institute (R21HL118588)
- National Cancer Institute (HHSN261200800001E), R01CA135341)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- K-Ras4B, GTP-bound Ras, Raf activation, RAF dimerization, dimer interface, switch I, effector binding, phosphatidylinositol 3-kinase, RalGDS, Ras effectors, cancer drug targets
- MeSH terms
- Guanosine Triphosphate, Humans, Kinetics, Protein Binding, Proto-Oncogene Proteins p21(ras), Catalytic Domain, Protein Interaction Domains and Motifs, Protein Multimerization
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
