The GDI-like solubilizing factor PDEδ sustains the spatial organization and signalling of Ras family proteins
Abstract
We identify a role for the GDI-like solubilizing factor (GSF) PDEδ in modulating signalling through Ras family G proteins by sustaining their dynamic distribution in cellular membranes. We show that the GDI-like pocket of PDEδ binds and solubilizes farnesylated Ras proteins, thereby enhancing their diffusion in the cytoplasm. This mechanism allows more effective trapping of depalmitoylated Ras proteins at the Golgi and polycationic Ras proteins at the plasma membrane to counter the entropic tendency to distribute these proteins over all intracellular membranes. Thus, PDEδ activity augments K/Hras signalling by enriching Ras at the plasma membrane; conversely, PDEδ down-modulation randomizes Ras distributions to all membranes in the cell and suppresses regulated signalling through wild-type Ras and also constitutive oncogenic Ras signalling in cancer cells. Our findings link the activity of PDEδ in determining Ras protein topography to Ras-dependent signalling.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
PDEδ is a protein that binds to KRAS protein and regulates its orientation to membrane compartments.
“PDEδ (phosphodiesterase 6 delta) is a protein that binds to KRAS protein and regulates its orientation to membrane compartments.337,338”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [337]
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
A new mathematical model for relative quantification in real-time RT-PCR
Pfaffl, M. W. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.9.e45 · Cited by 34,610 · see citing works
Membrane lipids: where they are and how they behave
van Meer, G., Voelker, D. R., & Feigenson, G. W. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2330 · Cited by 7,157 · see citing works
Shaner, N. C., Campbell, R. E., Steinbach, P. A., Giepmans, B. N. G., Palmer, A. E., & Tsien, R. Y. (2004) · Nature Biotechnology · doi:10.1038/nbt1037 · Cited by 4,619 · see citing works
Mobility measurement by analysis of fluorescence photobleaching recovery kinetics
Axelrod, D., Koppel, D. E., Schlessinger, J., Elson, E. L., & Webb, W. W. (1976) · Biophysical Journal · doi:10.1016/s0006-3495(76)85755-4 · Cited by 2,717 · see citing works
Hingorani, S. R., Wang, L., Multani, A. S., Combs, C., Deramaudt, T. B., Hruban, R. H., Rustgi, A. K., Chang, S., & Tuveson, D. A. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.04.023 · Cited by 2,609 · see citing works
Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse
Hingorani, S. R., Petricoin, E. F., Maitra, A., Rajapakse, V., King, C., Jacobetz, M. A., Ross, S., Conrads, T. P., Veenstra, T. D., Hitt, B. A., et al. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00309-x · Cited by 2,471 · see citing works
A Photoactivatable GFP for Selective Photolabeling of Proteins and Cells
Patterson, G. H., & Lippincott‐Schwartz, J. (2002) · Science · doi:10.1126/science.1074952 · Cited by 1,612 · see citing works
Fluorescence correlation spectroscopy. I. Conceptual basis and theory
Elson, E. L., & Magde, D. (1974) · Biopolymers · doi:10.1002/bip.1974.360130102 · Cited by 1,436 · see citing works
Membrane Phosphatidylserine Regulates Surface Charge and Protein Localization
Yeung, T., Gilbert, G. E., Shi, J., Silvius, J. R., Kapùs, A., & Grinstein, S. (2008) · Science · doi:10.1126/science.1152066 · Cited by 1,109 · see citing works
CHAFFEY, N. J. (2001) · Trends in Plant Science · doi:10.1016/s1360-1385(01)01902-1 · Cited by 1,043 · see citing works
Reducing the Environmental Sensitivity of Yellow Fluorescent Protein
Griesbeck, O., Baird, G. S., Campbell, R. E., Zacharias, D. A., & Tsien, R. Y. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102815200 · Cited by 1,023 · see citing works
An Acylation Cycle Regulates Localization and Activity of Palmitoylated Ras Isoforms
Rocks, O., Peyker, A., Kahms, M., Verveer, P., Koerner, C., Lumbierres, M., Kuhlmann, J., Waldmann, H., Wittinghofer, A., & Bastiaens, P. (2005) · Science · doi:10.1126/science.1105654 · Cited by 866 · see citing works
Self-citationSingh, A., Greninger, P., Rhodes, D., Koopman, L., Violette, S., Bardeesy, N., & Settleman, J. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.03.022 · Cited by 841 · see citing works
Human RAS Superfamily Proteins and Related GTPases
Colicelli, J. (2004) · Science s STKE · doi:10.1126/stke.2502004re13 · Cited by 837 · see citing works
Tuveson, D. A., Shaw, A. T., Willis, N. A., Silver, D. P., Jackson, E. L., Chang, S., Mercer, K. L., Grochow, R., Hock, H., Crowley, D., et al. (2004) · Cancer Cell · doi:10.1016/s1535-6108(04)00085-6 · Cited by 798 · see citing works
PI(3,4,5)P 3 and PI(4,5)P 2 Lipids Target Proteins with Polybasic Clusters to the Plasma Membrane
Heo, W. D., Inoue, T., Park, W. S., Kim, M. L., Park, B. O., Wandless, T. J., & Meyer, T. (2006) · Science · doi:10.1126/science.1134389 · Cited by 775 · see citing works
Endomembrane Trafficking of Ras
Choy, E., Chiu, V. K., Silletti, J., Feoktistov, M., Morimoto, T., Michaelson, D., Ivanov, I. E., & Philips, M. R. (1999) · Cell · doi:10.1016/s0092-8674(00)80607-8 · Cited by 754 · see citing works
Fluorescence Correlation Spectroscopy
(2011) · SpringerReference · doi:10.1007/springerreference_33960 · Cited by 714 · see citing works
Regulation of transbilayer plasma membrane phospholipid asymmetry
Daleke, D. L. (2003) · Journal of Lipid Research · doi:10.1194/jlr.r200019-jlr200 · Cited by 570 · see citing works
Dose-dependent oncogene-induced senescence in vivo and its evasion during mammary tumorigenesis
Sarkisian, C. J., Keister, B. A., Stairs, D. B., Boxer, R. B., Moody, S. E., & Chodosh, L. A. (2007) · Nature Cell Biology · doi:10.1038/ncb1567 · Cited by 490 · see citing works
Webb, Y., Hermida-Matsumoto, L., & Resh, M. D. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.1.261 · Cited by 475 · see citing works
Bivona, T. G., Quatela, S. E., Bodemann, B. O., Ahearn, I. M., Soskis, M. J., Mor, A., Miura, J., Wiener, H. H., Wright, L. P., Saba, S. G., et al. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.01.012 · Cited by 467 · see citing works
Imaging biochemistry inside cells
Wouters, F. S., Verveer, P. J., & Bastiaens, P. I. H. (2001) · Trends in Cell Biology · doi:10.1016/s0962-8924(01)01982-1 · Cited by 455 · see citing works
Self-citationThe Palmitoylation Machinery Is a Spatially Organizing System for Peripheral Membrane Proteins
Rocks, O., Gerauer, M., Vartak, N., Koch, S., Huang, Z., Pechlivanis, M., Kuhlmann, J., Brunsveld, L., Chandra, A., Ellinger, B., et al. (2010) · Cell · doi:10.1016/j.cell.2010.04.007 · Cited by 454 · see citing works
Self-citationH-ras but Not K-ras Traffics to the Plasma Membrane through the Exocytic Pathway
Apolloni, A., Prior, I. A., Lindsay, M. R., Parton, R. G., & Hancock, J. F. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.7.2475-2487.2000 · Cited by 416 · see citing works
Small-molecule inhibition of APT1 affects Ras localization and signaling.
Dekker, F., Rocks, O., Vartak, N., Menninger, S., Hedberg, C., Balamurugan, R., Wetzel, S., Renner, S., Gerauer, M., Schölermann, B., et al. (2010) · Nature Chemical Biology · doi:10.1038/nchembio.362 · Cited by 401 · see citing works
Self-citationGalectin-1 binds oncogenic H-Ras to mediate Ras membrane anchorage and cell transformation
Paz, A., Haklai, R., Elad‐Sfadia, G., Ballan, E., & Kloog, Y. (2001) · Oncogene · doi:10.1038/sj.onc.1204950 · Cited by 400 · see citing works
Purification and properties of a palmitoyl-protein thioesterase that cleaves palmitate from H-Ras.
Camp, L. A., & Hofmann, S. L. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)41567-0 · Cited by 362 · see citing works
Labeling and quantifying sites of protein palmitoylation
Drisdel, R. C., & Green, W. N. (2004) · BioTechniques · doi:10.2144/04362rr02 · Cited by 341 · see citing works
Context-Dependent Transformation of Adult Pancreatic Cells by Oncogenic K-Ras
Friedlander, S., Chu, G. C., Snyder, E. L., Girnius, N., Dibelius, G., Crowley, D. G., Vasile, E., DePinho, R. A., & Jacks, T. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.09.027 · Cited by 338 · see citing works
Receptor Activation Alters Inner Surface Potential During Phagocytosis
Yeung, T., Terebiznik, M., Yu, L., Silvius, J., Abidi, W. M., Philips, M., Levine, T., Kapus, A., & Grinstein, S. (2006) · Science · doi:10.1126/science.1129551 · Cited by 329 · see citing works
Depalmitoylated Ras traffics to and from the Golgi complex via a nonvesicular pathway
Goodwin, J., Drake, K. R., Rogers, C., Wright, L. P., Lippincott-Schwartz, J., Philips, M., & Kenworthy, A. (2005) · Journal of Cell Biology · doi:10.1083/jcb.200502063 · Cited by 308 · see citing works
Elad-Sfadia, G., Haklai, R., Balan, E., & Kloog, Y. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312697200 · Cited by 305 · see citing works
Arl2-GTP and Arl3-GTP regulate a GDI-like transport system for farnesylated cargo
Ismail, S. A., Chen, Y.-X., Rusinova, A., Chandra, A., Bierbaum, M., Gremer, L., Triola, G., Waldmann, H., Bastiaens, P. I. H., & Wittinghofer, A. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.686 · Cited by 252 · see citing works
Self-citationWilliamson, P., & Schlegel, R. (1994) · Molecular Membrane Biology · doi:10.3109/09687689409160430 · Cited by 240 · see citing works
The complex of Arl2‐GTP and PDEδ: from structure to function
Hanzal‐Bayer, M., Renault, L., Roversi, P., Wittinghofer, A., & Hillig, R. C. (2002) · The EMBO Journal · doi:10.1093/emboj/21.9.2095 · Cited by 222 · see citing works
Self-citationKim, J., Shishido, T., Jiang, X., Aderem, A. A., & McLaughlin, S. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)46916-5 · Cited by 186 · see citing works
Gosser, Y. Q., Nomanbhoy, T. K., Aghazadeh, B., Manor, D., Combs, C., Cerione, R. A., & Rosen, M. K. (1997) · Nature · doi:10.1038/42961 · Cited by 170 · see citing works
Skoulidis, F., Cassidy, L. D., Pisupati, V., Jonasson, J. G., Bjarnason, H., Eyfjord, J. E., Karreth, F. A., Lim, M., Barber, L. M., Clatworthy, S. A., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.10.015 · Cited by 167 · see citing works
Self-citationZhang, H., Li, S., Doan, T. A., Rieke, F. M., Detwiler, P. B., Frederick, J. M., & Baehr, W. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701681104 · Cited by 160 · see citing works
Yeung, T., Heit, B., Dubuisson, J.-F., Fairn, G. D., Chiu, B., Inman, R. D., Kapùs, A., Swanson, M. S., & Grinstein, S. (2009) · The Journal of Cell Biology · doi:10.1083/jcb.200903020 · Cited by 144 · see citing works
Photoreceptor cGMP Phosphodiesterase δ Subunit (PDEδ) Functions as a Prenyl-binding Protein
Zhang, H., Liu, X., Zhang, K., Chen, C.-K., Frederick, J. M., Prestwich, G. D., & Baehr, W. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306559200 · Cited by 126 · see citing works
Nancy, V., Callebaut, I., Marjou, A. E., & de Gunzburg, J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109983200 · Cited by 124 · see citing works
Lopez, A., Dupou, L., Altibelli, A., et al. (1988) · Biophysical Journal · doi:10.1016/s0006-3495(88)83177-1 · Cited by 102 · see citing works
Schreiber, F. S., Deramaudt, T. B., Brunner, T. B., Boretti, M. I., Gooch, K. J., Stoffers, D. A., Bernhard, E. J., & Rustgi, A. K. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.03.058 · Cited by 102 · see citing works
Transmembrane Topology of the Protein Palmitoyl Transferase Akr1
Politis, E. G., Roth, A. F., & Davis, N. G. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m411946200 · Cited by 94 · see citing works
Florio, S. K., Prusti, R. K., & Beavo, J. A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.39.24036 · Cited by 91 · see citing works
Global analysis of time correlated single photon counting FRET-FLIM data
Grecco, H. E., Roda‐Navarro, P., & Verveer, P. J. (2009) · Optics Express · doi:10.1364/oe.17.006493 · Cited by 90 · see citing works
Self-citationSynthesis of the Rheb and K‐Ras4B GTPases
Chen, Y., Koch, S., Uhlenbrock, K., Weise, K., Das, D., Gremer, L., Brunsveld, L., Wittinghofer, A., Winter, R., Triola, G., et al. (2010) · Angewandte Chemie International Edition · doi:10.1002/anie.201001884 · Cited by 76 · see citing works
Self-citationLongenecker, K. L., Read, P. W., Derewenda, U., et al. (1999) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s090744499900801x · Cited by 75 · see citing works
Imaging Activation of Two Ras Isoforms Simultaneously in a Single Cell
Lorentzen, A., Rocks, O., & Bastiaens, P. I. H. (2005) · ChemBioChem · doi:10.1002/cbic.200400280 · Cited by 68 · see citing works
Self-citationThe Rod cGMP Phosphodiesterase δ Subunit Dissociates the Small GTPase Rab13 from Membranes
Marzesco, A., Galli, T., Louvard, D., & Zahraoui, A. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.35.22340 · Cited by 63 · see citing works
Multiple Cellular Proteins Modulate the Dynamics of K-ras Association with the Plasma Membrane
Bhagatji, P., Leventis, R., Rich, R. L., Lin, C., & Silvius, J. R. (2010) · Biophysical Journal · doi:10.1016/j.bpj.2010.10.001 · Cited by 51 · see citing works
Regulation of Ras Localization by Acylation Enables a Mode of Intracellular Signal Propagation
Lorentzen, A., Kinkhabwala, A., Rocks, O., Vartak, N., & Bastiaens, P. (2010) · Science Signaling · doi:10.1126/scisignal.20001370 · Cited by 51 · see citing works
Self-citationFarrell, F. X., Yamamoto, K., & Lapetina, E. G. (1993) · Biochemical Journal · doi:10.1042/bj2890349 · Cited by 46 · see citing works
Richards, C. A., Short, S. A., Thorgeirsson, S. S., et al. (1990) · PubMed · Cited by 36 · see citing works
Isoprenylation of rap2 proteins in platelets and human erythroleukemia cells
Winegar, D. A., Vedia, L. M. Y., & Lapetina, E. G. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)64333-2 · Cited by 27 · see citing works
Wilson, S. J., & Smyth, E. M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m513110200 · Cited by 20 · see citing works
Lorenz, B., Migliaccio, C., Lichtner, P., et al. (1998) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5200215 · Cited by 16 · see citing works
Mapping the Isoprenoid Binding Pocket of PDEδ by a Semisynthetic, Photoactivatable N‐Ras Lipoprotein
Alexander, M., Gerauer, M., Pechlivanis, M., et al. (2008) · ChemBioChem · doi:10.1002/cbic.200800275 · Cited by 15 · see citing works
Sang, S. L. W., & Silvius, J. R. (2005) · Journal of Peptide Research · doi:10.1111/j.1399-3011.2005.00285.x · Cited by 12 · see citing works
[Pancreatic resection for metastatic renal cell carcinoma].
Varga, M., Oliverius, M., Valsamis, A., et al. (2009) · PubMed · Cited by 1 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
RAS Proteins and Their Regulators in Human Disease
Simanshu, D. K., Nissley, D. V., & McCormick, F. (2017) · Cell · doi:10.1016/j.cell.2017.06.009 · Cited by 1,943 · see citing works
Drugging the undruggable RAS: Mission Possible?
Cox, A. D., Fesik, S. W., Kimmelman, A. C., Luo, J., & Der, C. J. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4389 · Cited by 1,997 · see citing works
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 · see citing works
Lu, H., Zhou, Q., He, J., Jiang, Z., Peng, C., Tong, R., & Shi, J. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00315-3 · Cited by 891 · see citing works
Small molecule inhibition of the KRAS–PDEδ interaction impairs oncogenic KRAS signalling
Zimmermann, G., Papke, B., Ismail, S., Vartak, N., Chandra, A., Hoffmann, M., Hahn, S. A., Triola, G., Wittinghofer, A., Bastiaens, P. I. H., et al. (2013) · Nature · doi:10.1038/nature12205 · Cited by 596 · see citing works
Self-citationGenetics and biology of pancreatic ductal adenocarcinoma
Ying, H., Dey, P., Yao, W., Kimmelman, A. C., Draetta, G. F., Maitra, A., & DePinho, R. A. (2016) · Genes & Development · doi:10.1101/gad.275776.115 · Cited by 527 · see citing works
Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials
Xie, X., Yu, T., Li, X., Zhang, N., Foster, L. J., Peng, C., Huang, W., & He, G. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01589-z · Cited by 396 · see citing works
Targeting the untargetable KRAS in cancer therapy
Liu, P., Wang, Y., & Li, X. (2019) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2019.03.002 · Cited by 366 · see citing works
Targeting RAS Membrane Association: Back to the Future for Anti-RAS Drug Discovery?
Cox, A. D., Der, C. J., & Philips, M. R. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-3214 · Cited by 351 · see citing works
Autopalmitoylation of TEAD proteins regulates transcriptional output of the Hippo pathway
Chan, P., Han, X., Zheng, B., DeRan, M., Yu, J., Jarugumilli, G. K., Deng, H., Pan, D., Luo, X., & Wu, X. (2016) · Nature Chemical Biology · doi:10.1038/nchembio.2036 · Cited by 313 · see citing works
Therapeutic Targeting of Oncogenic K‐Ras by a Covalent Catalytic Site Inhibitor
Lim, S. M., Westover, K. D., Ficarro, S. B., Harrison, R. A., Choi, H. G., Pacold, M. E., Carrasco, M., Hunter, J., Kim, N. D., Xie, T., et al. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201307387 · Cited by 300 · see citing works
PROTACs: great opportunities for academia and industry (an update from 2020 to 2021)
He, M., Cao, C., Ni, Z., Liu, Y., Song, P., Hao, S., He, Y., Sun, X., & Rao, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00999-9 · Cited by 283 · see citing works
Schmick, M., Vartak, N., Papke, B., Kovacevic, M., Truxius, D. C., Rossmannek, L., & Bastiaens, P. I. H. (2014) · Cell · doi:10.1016/j.cell.2014.02.051 · Cited by 243 · see citing works
Self-citationKRAS G12C Game of Thrones, which direct KRAS inhibitor will claim the iron throne?
Nagasaka, M., Li, Y., Sukari, A., Ou, S.-H. I., Al-Hallak, M. N., & Azmi, A. S. (2020) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2020.101974 · Cited by 185 · see citing works
RAS: Striking at the Core of the Oncogenic Circuitry
Gimple, R. C., & Wang, X. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00965 · Cited by 174 · see citing works
Pharmacological targeting of RAS: recent success with direct inhibitors
O’Bryan, J. P. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2018.10.021 · Cited by 153 · see citing works
Ntai, I., Fornelli, L., DeHart, C. J., Hutton, J. E., Doubleday, P. F., LeDuc, R. D., van Nispen, A. J., Fellers, R. T., Whiteley, G., Boja, E. S., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1716122115 · Cited by 108 · see citing works
A RAS Renaissance: Emerging Targeted Therapies for KRAS-Mutated Non–Small Cell Lung Cancer
Vasan, N., Boyer, J. L., & Herbst, R. S. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-1762 · Cited by 102 · see citing works
Intrinsically disordered proteins and membranes: a marriage of convenience for cell signalling?
Cornish, J., Chamberlain, S. G., Owen, D., & Mott, H. R. (2020) · Biochemical Society Transactions · doi:10.1042/bst20200467 · Cited by 69 · see citing works
Development of PDE6D and CK1α Degraders through Chemical Derivatization of FPFT-2216
Teng, M., Lu, W., Donovan, K. A., Sun, J., Krupnick, N. M., Nowak, R. P., Li, Y.-D., Sperling, A. S., Zhang, T., Ebert, B. L., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01832 · Cited by 63 · see citing works
Development of covalent inhibitors: Principle, design, and application in cancer
Zheng, L., Li, Y., Wu, D., Xiao, H., Zheng, S., Wang, G., & Sun, Q. (2023) · MedComm – Oncology · doi:10.1002/mog2.56 · Cited by 71 · see citing works
PDE6D Inhibitors with a New Design Principle Selectively Block K-Ras Activity
Siddiqui, F. A., Alam, C., Rosenqvist, P., Ora, M., Sabt, A., Manoharan, G. B., Bindu, L., Okutachi, S., Catillon, M., Taylor, T., et al. (2020) · ACS Omega · doi:10.1021/acsomega.9b03639 · Cited by 46 · see citing works
Efforts to Develop KRAS Inhibitors
Holderfield, M. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a031864 · Cited by 43 · see citing works
Leung, E. L., Luo, L. X., Li, Y., Liu, Z., Li, L. L., Shi, D. F., Xie, Y., Huang, M., Lu, L. L., Duan, F. G., et al. (2019) · International Journal of Cancer · doi:10.1002/ijc.32222 · Cited by 39 · see citing works
Discovery of Novel KRAS-PDEδ Inhibitors by Fragment-Based Drug Design
Chen, L., Zhuang, C., Lu, J., Jiang, Y., & Sheng, C. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00057 · Cited by 33 · see citing works
Structural Biology-Inspired Discovery of Novel KRAS–PDEδ Inhibitors
Jiang, Y., Zhuang, C., Chen, L., Lu, J., Dong, G., Miao, Z., Zhang, W., Li, J., & Sheng, C. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b01243 · Cited by 34 · see citing works
Oncogenic KRAS engages an RSK1/NF1 pathway to inhibit wild-type RAS signaling in pancreatic cancer
Cheng, D. K., Oni, T. E., Thalappillil, J. S., Park, Y., Ting, H.-C., Alagesan, B., Prasad, N. V., Addison, K., Rivera, K. D., Pappin, D. J., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2016904118 · Cited by 30 · see citing works
Fragment-based drug discovery of triazole inhibitors to block PDEδ-RAS protein-protein interaction
Chen, D., Chen, Y., Lian, F., Chen, L., Li, Y., Cao, D., Wang, X., Chen, L., Li, J., Meng, T., et al. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.12.018 · Cited by 31 · see citing works
Therapeutic Targets of KRAS in Colorectal Cancer
Rahman, S., Garrel, S., Gerber, M., Maitra, R., & Goel, S. (2021) · Cancers · doi:10.3390/cancers13246233 · Cited by 28 · see citing works
Chen, L., Zhang, J., Wang, X., Li, Y., Zhou, L., Lu, X., Dong, G., & Sheng, C. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.07.009 · Cited by 20 · see citing works
- Authors
- Chandra, A., Grecco, H. E., Pisupati, V., Perera, D., Cassidy, L., Skoulidis, F., Ismail, S. A., Hedberg, C., Hanzal-Bayer, M., Venkitaraman, A. R., Wittinghofer, A., & Bastiaens, P. I. H.
- Affiliations
- Max Planck Institute of Molecular Physiology (DE)
- MRC Cancer Unit (GB)
- TU Dortmund University (DE)
- Corresponding author
- Bastiaens, Philippe I. H.
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2011-12-18
- Volume
- 14
- Issue
- 2
- Pages
- 148-158
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2069537707
- Cited by
- 325
- References
- 63
- Citations by year
- 2026: 14 · 2025: 8 · 2024: 18 · 2023: 18 · 2022: 18 · 2021: 35 · 2020: 26 · 2019: 23 · 2018: 24 · 2017: 35 · 2016: 25 · 2015: 16 · 2014: 28 · 2013: 21 · 2012: 14
- FWCI
- 8.32
- Type
- journal article
- Language
- en
- Update notices
- erratum (2012-02-29)
- Open access
- closed
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- National Institute for Health and Care Research (CL-2008-14-003)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Keywords
- PDEδ, Ras family GTPases, membrane protein distribution, Golgi apparatus, plasma membrane, Ras signaling, oncogenic Ras, subcellular localization, protein diffusion
- MeSH terms
- Amino Acid Sequence, Animals, Cell Line, Cell Membrane, Golgi Apparatus, Humans, Intracellular Membranes, Molecular Sequence Data, Protein Binding, Blotting, Western, Signal Transduction, Microscopy, Confocal, ras Proteins, GTP-Binding Proteins, Guanine Nucleotide Dissociation Inhibitors, Fluorescence Resonance Energy Transfer, RNA Interference, Fluorescence Recovery After Photobleaching, Green Fluorescent Proteins, Cyclic Nucleotide Phosphodiesterases, Type 6, Prenylation, Lipoylation, Hep G2 Cells
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