Label-free quantitative phosphoproteomics with novel pairwise abundance normalization reveals synergistic RAS and CIP2A signaling
Open accessAbstract
Hyperactivated RAS drives progression of many human malignancies. However, oncogenic activity of RAS is dependent on simultaneous inactivation of protein phosphatase 2A (PP2A) activity. Although PP2A is known to regulate some of the RAS effector pathways, it has not been systematically assessed how these proteins functionally interact. Here we have analyzed phosphoproteomes regulated by either RAS or PP2A, by phosphopeptide enrichment followed by mass-spectrometry-based label-free quantification. To allow data normalization in situations where depletion of RAS or PP2A inhibitor CIP2A causes a large uni-directional change in the phosphopeptide abundance, we developed a novel normalization strategy, named pairwise normalization. This normalization is based on adjusting phosphopeptide abundances measured before and after the enrichment. The superior performance of the pairwise normalization was verified by various independent methods. Additionally, we demonstrate how the selected normalization method influences the downstream analyses and interpretation of pathway activities. Consequently, bioinformatics analysis of RAS and CIP2A regulated phosphoproteomes revealed a significant overlap in their functional pathways. This is most likely biologically meaningful as we observed a synergistic survival effect between CIP2A and RAS expression as well as KRAS activating mutations in TCGA pan-cancer data set and synergistic relationship between CIP2A and KRAS depletion in colony growth assays.
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CIP2A overexpression is an equally strong predictor of poor survival in TCGA pan-cancer data as KRAS mutation.
“CIP2A overexpression is an equally strong predictor of poor survival in TCGA pan-cancer data as KRAS mutation”
From Oncoprotein CIP2A is stabilized via interaction with tumor suppressor PP2A/B56 (2017) · cites this paper as [13]
The Results section (page unavailable) associates high CIP2A expression with poor prognosis in TCGA pan-cancer data and reports poor survival among KRAS mutants. It also describes a synergistic survival effect, but does not establish that CIP2A overexpression and KRAS mutation are equally strong predictors. (LLM, conf=0.84)
Experimental — accuracy not yet measuredBinding of CIP2A to PP2A via specific B subunits may explain why CIP2A only regulates a fairly restricted number of phosphoproteins among thousands of potential target proteins regulated by different PP2A complexes.
“Binding of CIP2A to PP2A via specific B subunits imposes an interesting possible explanation for observations that CIP2A only regulates a fairly restricted number of phosphoproteins [6,13] among thousands of potential target proteins regulated by different PP2A complexes [24,26].”
From Oncoprotein CIP2A is stabilized via interaction with tumor suppressor PP2A/B56 (2017) · cites this paper as [13]
The Discussion (page unavailable) reports an analysis of phosphoproteins regulated by CIP2A, and the Results (page unavailable) identify 2,911 measured phosphosites on 1,255 proteins. Our copy does not establish that CIP2A regulates only a fairly restricted number relative to PP2A’s potential targets. The proposed explanation involving specific PP2A B subunits is the citing authors’ framing, not a finding attributed to this source by the attached citation. (LLM, conf=0.72)
Experimental — accuracy not yet measuredPatients with both CIP2A overexpression and KRAS mutation constitute the patient population with clearly the worst outcome.
“the patients with both of these alterations constituted the patient population with clearly the worst outcome [13]”
From Oncoprotein CIP2A is stabilized via interaction with tumor suppressor PP2A/B56 (2017) · cites this paper as [13]
There is significant overlap between CIP2A and RAS-regulated phosphoproteomes.
“we recently demonstrated significant overlap between CIP2A and RAS-regulated phosphoproteomes [13]”
From Oncoprotein CIP2A is stabilized via interaction with tumor suppressor PP2A/B56 (2017) · cites this paper as [13]
CIP2A impacts oncogenic RAS signaling and MYC activity in vivo.
“Impact of CIP2A on both oncogenic RAS signaling [10,13,36] and MYC activity in vivo [10,12,22]”
From Oncoprotein CIP2A is stabilized via interaction with tumor suppressor PP2A/B56 (2017) · cites this paper as [13]
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Cites
Ong, S.-E., Blagoev, B., Kratchmarova, I., Kristensen, D. B., Steen, H., Pandey, A., & Mann, M. (2002) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m200025-mcp200 · Cited by 5,574 · see citing works
Ross, P. L., Huang, Y. N., Marchese, J. N., Williamson, B., Parker, K., Hattan, S., Khainovski, N., Pillai, S., Dey, S., Daniels, S., et al. (2004) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m400129-mcp200 · Cited by 4,401 · see citing works
Global, In Vivo, and Site-Specific Phosphorylation Dynamics in Signaling Networks
Olsen, J. V., Blagoev, B., Gnad, F., Maček, B., Kumar, C., Mortensen, P., & Mann, M. (2006) · Cell · doi:10.1016/j.cell.2006.09.026 · Cited by 3,484 · see citing works
Targeting RAS signalling pathways in cancer therapy
Downward, J. (2003) · Nature reviews. Cancer · doi:10.1038/nrc969 · Cited by 3,262 · see citing works
Protein kinases and phosphatases: The Yin and Yang of protein phosphorylation and signaling
Hunter, T. R. (1995) · Cell · doi:10.1016/0092-8674(95)90405-0 · Cited by 2,959 · see citing works
ProteomeXchange provides globally coordinated proteomics data submission and dissemination
Vizcaíno, J. A., Deutsch, E. W., Wang, R., Csordás, A., Reisinger, F., Ríos, D., Dianes, J. A., Sun, Z., Farrah, T., Bandeira, N., et al. (2014) · Nature Biotechnology · doi:10.1038/nbt.2839 · Cited by 2,735 · see citing works
Targeting cancer with small molecule kinase inhibitors
Zhang, J., Yang, P. L., & Gray, N. S. (2008) · Nature reviews. Cancer · doi:10.1038/nrc2559 · Cited by 2,586 · see citing works
A 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 · see citing works
Pan-cancer patterns of somatic copy number alteration
Zack, T. I., Schumacher, S. E., Carter, S. L., Cherniack, A. D., Saksena, G., Tabak, B., Lawrence, M. S., Zhang, C., Wala, J. A., Mermel, C. H., et al. (2013) · Nature Genetics · doi:10.1038/ng.2760 · Cited by 1,843 · see citing works
Bialojan, C., & Takai, A. (1988) · Biochemical Journal · doi:10.1042/bj2560283 · Cited by 1,703 · see citing works
Hornbeck, P. V., Kornhauser, J. M., Tkachev, S., Zhang, B., Skrzypek, E., Murray, B. W., Latham, V. M., & Sullivan, M. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr1122 · Cited by 1,636 · see citing works
A quantitative atlas of mitotic phosphorylation
Dephoure, N., Zhou, C., Villén, J., Beausoleil, S. A., Bakalarski, C. E., Elledge, S. J., & Gygi, S. P. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805139105 · Cited by 1,608 · see citing works
Protein Analysis by Shotgun/Bottom-up Proteomics
Zhang, Y., Fonslow, B. R., Shan, B., Baek, M.-C., & Yates, J. R. (2013) · Chemical Reviews · doi:10.1021/cr3003533 · Cited by 1,491 · see citing works
Larsen, M. R., Thingholm, T. E., Jensen, O. N., Roepstorff, P., & Jørgensen, T. J. D. (2005) · Molecular & Cellular Proteomics · doi:10.1074/mcp.t500007-mcp200 · Cited by 1,478 · see citing works
Multiple Ras-dependent phosphorylation pathways regulate Myc protein stabilityPreprint
Sears, R. C., Nuckolls, F., Haura, E. B., Taya, Y., Tamai, K., & Nevins, J. R. (2000) · Genes & Development · doi:10.1101/gad.836800 · Cited by 1,379 · see citing works
Sharma, K., D’Souza, R. C. J., Tyanova, S., Schaab, C., Wiśniewski, J. R., Cox, J., & Mann, M. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.07.036 · Cited by 971 · see citing works
Universal and Confident Phosphorylation Site Localization Using phosphoRS
Taus, T., Köcher, T., Pichler, P., Paschke, C., Schmidt, A., Henrich, C., & Mechtler, K. (2011) · Journal of Proteome Research · doi:10.1021/pr200611n · Cited by 875 · see citing works
Roux, P. P., Shahbazian, D., Vu, H., Holz, M. K., Cohen, M. S., Taunton, J., Sonenberg, N., & Blenis, J. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700906200 · Cited by 749 · see citing works
ColonyArea: An ImageJ Plugin to Automatically Quantify Colony Formation in Clonogenic Assays
Guzmán, C., Bagga, M., Kaur, A., Westermarck, J. K., & Abankwa, D. (2014) · PLoS ONE · doi:10.1371/journal.pone.0092444 · Cited by 720 · see citing works
Self-citationCIP2A inhibits PP2A in human malignancies
Junttila, M. R., Puustinen, P., Niemelä, M., Ahola, R., Arnold, H., Böttzauw, T., Ala-aho, R., Nielsen, C., Ivaska, J., Taya, Y., et al. (2007) · Cell · doi:10.1016/j.cell.2007.04.044 · Cited by 677 · see citing works
Self-citationGPS 2.0, a Tool to Predict Kinase-specific Phosphorylation Sites in Hierarchy
Xue, Y., Ren, J. M., Gao, X., Jin, C., Wen, L., & Yao, X. (2008) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m700574-mcp200 · Cited by 628 · see citing works
Enumeration of the Simian Virus 40 Early Region Elements Necessary for Human Cell Transformation
Hahn, W. C., Dessain, S. K., Brooks, M. W., King, J. E., Elenbaas, B., Sabatini, D. M., DeCaprio, J. A., & Weinberg, R. A. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.7.2111-2123.2002 · Cited by 603 · see citing works
Regulation of protein serine-threonine phosphatase type-2A by tyrosine phosphorylation
Chen, J., Martin, B. L., & Brautigan, D. L. (1992) · Science · doi:10.1126/science.1325671 · Cited by 601 · see citing works
Species- and cell type-specific requirements for cellular transformation
Rangarajan, A., Hong, S. J., Gifford, A., & Weinberg, R. A. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.07.009 · Cited by 555 · see citing works
Protein phosphatase 2A regulatory subunits and cancer
Eichhorn, P. J. A., Creyghton, M. P., & Bernards, R. (2009) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2008.05.005 · Cited by 513 · see citing works
Sontag, E., Fedorov, S. A., Kamibayashi, C., Robbins, D. J., Cobb, M. H., & Mumby, M. C. (1993) · Cell · doi:10.1016/0092-8674(93)90533-v · Cited by 510 · see citing works
Interpreting the protein language using proteomics
Jensen, O. N. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1939 · Cited by 505 · see citing works
Peterson, R., Desai, B. N., Hardwick, J. S., & Schreiber, S. (1999) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.96.8.4438 · Cited by 496 · see citing works
Oncogenic K‐Ras decouples glucose and glutamine metabolism to support cancer cell growth
Gaglio, D., Metallo, C. M., Gameiro, P. A., Hiller, K., Danna, L. S., Balestrieri, C., Alberghina, L., Stephanopoulos, G., & Chiaradonna, F. (2011) · Molecular Systems Biology · doi:10.1038/msb.2011.56 · Cited by 492 · see citing works
Ras oncogenes and their downstream targets
Rajalingam, K., Schreck, R., Rapp, U. R., & Albert, Š. (2007) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2007.01.012 · Cited by 458 · see citing works
Casado, P., Rodríguez‐Prados, J., Cosulich, S. C., Guichard, S. M., Vanhaesebroeck, B., Joel, S., & Cutillas, P. R. (2013) · Science Signaling · doi:10.1126/scisignal.2003573 · Cited by 411 · see citing works
Multiple pathways regulated by the tumor suppressor PP2A in transformation
Westermarck, J., & Hahn, W. C. (2008) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2008.02.001 · Cited by 344 · see citing works
Self-citationQuantitative maps of protein phosphorylation sites across 14 different rat organs and tissues
Lundby, A., Secher, A., Lage, K., Nordsborg, N. B., Dmytriyev, A., Lundby, C., & Olsen, J. V. (2012) · Nature Communications · doi:10.1038/ncomms1871 · Cited by 341 · see citing works
KinomeXplorer: an integrated platform for kinome biology studies
Horn, H., Schoof, E. M., Kim, J., Robin, X., Miller, M. L., Diella, F., Palma, A., Cesareni, G., Jensen, L. J., & Linding, R. (2014) · Nature Methods · doi:10.1038/nmeth.2968 · Cited by 338 · see citing works
PP2A: Unveiling a Reluctant Tumor Suppressor
Mumby, M. (2007) · Cell · doi:10.1016/j.cell.2007.06.034 · Cited by 295 · see citing works
Swingle, M. R., Ni, L., & Honkanen, R. E. (2007) · Humana Press eBooks · doi:10.1385/1-59745-267-x:23 · Cited by 291 · see citing works
Human mammary epithelial cell transformation through the activation of phosphatidylinositol 3-kinase
Zhao, J. J., Gjoerup, O. V., Subramanian, R. R., Cheng, Y., Chen, W., Roberts, T. M., & Hahn, W. C. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00088-6 · Cited by 280 · see citing works
Exploring TCGA Pan-Cancer Data at the UCSC Cancer Genomics Browser
Cline, M., Craft, B., Swatloski, T., Goldman, M. J., Ma, S., Haussler, D. H., & Zhu, J. (2013) · Scientific Reports · doi:10.1038/srep02652 · Cited by 271 · see citing works
Protein kinase signaling networks in cancer
Brognard, J., & Hunter, T. R. (2010) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2010.10.012 · Cited by 240 · see citing works
Letourneux, C., Rocher, G., & Porteu, F. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7600980 · Cited by 224 · see citing works
Genetic Alterations in Signaling Pathways in Melanoma
Haluska, F. G., Tsao, H., Wu, H. L., Haluska, F. S., Lazar, A. J., & Goel, V. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-2518 · Cited by 194 · see citing works
Identification of PP2A Complexes and Pathways Involved in Cell Transformation
Sablina, A. A., Hector, M., Colpaert, N., & Hahn, W. C. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-2855 · Cited by 193 · see citing works
The UCSC Cancer Genomics Browser
Zhu, J., Sanborn, Z., Benz, S. C., Szeto, C. W., Hsu, F., Kuhn, R. M., Karolchik, D., Archie, J. G., Lenburg, M. E., Esserman, L. J., et al. (2009) · Nature Methods · doi:10.1038/nmeth0409-239 · Cited by 171 · see citing works
Technologies and challenges in large‐scale phosphoproteomics
Engholm‐Keller, K., & Larsen, M. R. (2013) · PROTEOMICS · doi:10.1002/pmic.201200484 · Cited by 167 · see citing works
CIP2A mediates effects of bortezomib on phospho-Akt and apoptosis in hepatocellular carcinoma cells
Chen, K.-F., Liu, C.-Y., Lin, Y.-C., Yu, H.-C., Liu, T.-H., Hou, D.-R., Chen, P.-J., & Cheng, A.-L. (2010) · Oncogene · doi:10.1038/onc.2010.357 · Cited by 152 · see citing works
Li, W., Ge, Z., Liu, C., Liu, Z., Björkholm, M., Jia, J., & Xu, D. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-4137 · Cited by 142 · see citing works
Lucas, C. M., Harris, R. J., Giannoudis, A., Copland, M., Slupsky, J. R., & Clark, R. E. (2011) · Blood · doi:10.1182/blood-2010-08-304477 · Cited by 138 · see citing works
Laine, A., Sihto, H., Come, C., Rosenfeldt, M. T., Zwolinska, A., Niemelä, M., Khanna, A., Chan, E. K., Kähäri, V.-M., Kellokumpu-Lehtinen, P.-L., et al. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0292 · Cited by 130 · see citing works
Self-citationCharacterization of a TiO2 enrichment method for label-free quantitative phosphoproteomics
Montoya, A., Beltran, L., Casado, P., Rodríguez‐Prados, J., & Cutillas, P. R. (2011) · Methods · doi:10.1016/j.ymeth.2011.02.004 · Cited by 115 · see citing works
Protein phosphatase 2A regulates life and death decisions via Akt in a context-dependent manner
Andrabi, S., Gjoerup, O. V., Kean, J. A., Roberts, T. M., & Schaffhausen, B. S. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706696104 · Cited by 104 · see citing works
Ras isoform abundance and signalling in human cancer cell lines
Omerović, J., Hammond, D. E., Clague, M. J., & Prior, I. A. (2007) · Oncogene · doi:10.1038/sj.onc.1210925 · Cited by 101 · see citing works
Prognostic role of CIP2A expression in serous ovarian cancer
Böckelman, C., Lassus, H., Hemmes, A., Leminen, A., Westermarck, J., Haglund, C., Bützow, R., & Ristimäki, A. (2011) · British Journal of Cancer · doi:10.1038/bjc.2011.346 · Cited by 100 · see citing works
Self-citationSV40 small T antigen and PP2A phosphatase in cell transformation
Sablina, A. A., & Hahn, W. C. (2008) · Cancer and Metastasis Reviews · doi:10.1007/s10555-008-9116-0 · Cited by 95 · see citing works
de Graaf, E. L., Giansanti, P., Altelaar, M. A. F., & Heck, A. J. R. (2014) · Molecular & Cellular Proteomics · doi:10.1074/mcp.o113.036608 · Cited by 95 · see citing works
Birkeland, E., Wik, E., Mjøs, S., Høivik, E. A., Trovik, J., Werner, H. M. J., Kusonmano, K., Petersen, K., Raeder, M. B., Holst, F., et al. (2012) · British Journal of Cancer · doi:10.1038/bjc.2012.477 · Cited by 84 · see citing works
Niemelä, M., Kauko, O., Sihto, H., Mpindi, J.-P., Nicorici, D., Pernilä, P., Kallioniemi, O.-P., Joensuu, H., Hautaniemi, S., & Westermarck, J. (2012) · Oncogene · doi:10.1038/onc.2011.599 · Cited by 79 · see citing works
Self-citationBlomster, H. A., Imanishi, S. Y., Joutsen, J., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.106955 · Cited by 77 · see citing works
Self-citationReference-facilitated Phosphoproteomics
Imanishi, S. Y., Kochin, V., Ferraris, S. E., de Thonel, A., Pallari, H., Corthals, G. L., & Eriksson, J. (2007) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m600480-mcp200 · Cited by 75 · see citing works
Self-citationNaetar, N., Soundarapandian, V., Litovchick, L., Goguen, K. L., Sablina, A. A., Bowman-Colin, C., Siciński, P., Hahn, W. C., DeCaprio, J. A., & Livingston, D. M. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.04.023 · Cited by 67 · see citing works
Wang, Y.-T., Tsai, C.-F., Hong, T.-C., Tsou, C.-C., Lin, P.-Y., Pan, S.-H., Hong, T., Yang, P.-C., Sung, T.-Y., Hsu, W.-L., et al. (2010) · Journal of Proteome Research · doi:10.1021/pr100394u · Cited by 66 · see citing works
Systems-wide Analysis of K-Ras, Cdc42, and PAK4 Signaling by Quantitative Phosphoproteomics
Gnad, F., Young, A. E., Zhou, W., Lyle, K. S., Ong, C. C., Stokes, M. P., Silva, J. C., Belvin, M. P., Friedman, L. S., Koeppen, H., et al. (2013) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m112.027052 · Cited by 51 · see citing works
Quantitative Label-Free Phosphoproteomics Strategy for Multifaceted Experimental Designs
Soderblom, E. J., Philipp, M., Thompson, J. W., Caron, M. G., & Moseley, M. A. (2011) · Analytical Chemistry · doi:10.1021/ac200213b · Cited by 47 · see citing works
Mathiasen, D. P., Egebjerg, C., Andersen, S. H., Rafn, B., Puustinen, P., Khanna, A., Daugaard, M., Valo, E., Tuomela, S., Bøttzauw, T., et al. (2012) · Oncogene · doi:10.1038/onc.2011.230 · Cited by 44 · see citing works
Self-citationYoung, T. W., Mei, F. C., Liu, J., Bast, R. C., Kurosky, A., & Cheng, X. (2005) · Oncogene · doi:10.1038/sj.onc.1208753 · Cited by 39 · see citing works
Sudhir, P., Hsu, C., Wang, M.-J., Wang, Y.-T., Chen, Y., Sung, T.-Y., Hsu, W.-L., Yang, U., & Chen, J.-Y. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020199 · Cited by 36 · see citing works
Quintaje, S. B., Church, D. J., Rebsamen, M. C., Vallotton, M. B., Hemmings, B. A., & Lang, U. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.0632 · Cited by 36 · see citing works
Manes, N. P., Li, D., Zhou, W., Du, X., Reghu, N., Kool, A. C., Choi, D., Bailey, C., Petricoin, E. F., Liotta, L. A., et al. (2010) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m110.000927 · Cited by 36 · see citing works
Zhou, X., Winblad, B. G., Guan, Z., & Pei, J.-J. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-1113 · Cited by 33 · see citing works
Mutations and Expression of the ras Family Genes in Leukemias
Gougopoulou, D. M., Kiaris, H., Ergazaki, M., Anagnostopoulos, N. I., Grigoraki, V., & Spandidos, D. A. (1996) · Stem Cells · doi:10.1002/stem.140725 · Cited by 31 · see citing works
Confident Site Localization Using a Simulated Phosphopeptide Spectral Library
Suni, V., Imanishi, S. Y., Maiolica, A., Aebersold, R. H., & Corthals, G. L. (2015) · Journal of Proteome Research · doi:10.1021/acs.jproteome.5b00050 · Cited by 29 · see citing works
Self-citationYang, F., Jaitly, N., Jayachandran, H., Luo, Q., Monroe, M. E., Du, X., Gritsenko, M. A., Zhang, R., Anderson, D. J., Purvine, S. O., et al. (2007) · Journal of Proteome Research · doi:10.1021/pr070068e · Cited by 24 · see citing works
Kim, S., Lee, Y. Z., Kim, Y. S., et al. (2008) · PROTEOMICS · doi:10.1002/pmic.200800106 · Cited by 16 · see citing works
Proteomics Analysis Reveals Insight into the Mechanism of H-Ras-Mediated Transformation
Jin, B., He, K., Wang, H., et al. (2006) · Journal of Proteome Research · doi:10.1021/pr060283f · Cited by 14 · see citing works
Öhman, T., Söderholm, S., Hintsanen, P., Välimäki, E., Lietzén, N., MacKintosh, C., Aittokallio, T. A., Matikainen, S., & Nyman, T. A. (2014) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m114.038968 · Cited by 10 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- Howlader N.. SEER Cancer Statistics Review, 1975-2011. National Cancer Institute. Bethesda, MD. (2014).
Cited by
Sorted by citations
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Kauko, O., O’Connor, C. M., Kulesskiy, E., Sangodkar, J., Aakula, A., Izadmehr, S., Yetukuri, L., Yadav, B., Padzik, A., Laajala, T. D., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aaq1093 · Cited by 149 · see citing works
Self-citationNon-genomic mechanisms of protein phosphatase 2A (PP2A) regulation in cancer
Kauko, O., & Westermarck, J. (2018) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2018.01.005 · Cited by 111 · see citing works
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Wang, J., Okkeri, J., Pavic, K., Wang, Z., Kauko, O., Halonen, T., Sarek, G., Ojala, P. M., Rao, Z., Xu, W., et al. (2017) · The EMBO Reports · doi:10.15252/embr.201642788 · Cited by 95 · see citing works
Self-citationKauko, O., Imanishi, S. Y., Kulesskiy, E., Yetukuri, L., Laajala, T. D., Sharma, M., Pavic, K., Aakula, A., Rupp, C., Jumppanen, M., et al. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.011265 · Cited by 65 · see citing works
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- Authors
- Kauko, O., Laajala, T. D., Jumppanen, M., Hintsanen, P., Suni, V., Haapaniemi, P., Corthals, G., Aittokallio, T., Westermarck, J., & Imanishi, S. Y.
- Affiliations
- Åbo Akademi University (FI)
- University of Turku (FI)
- Institute for Molecular Medicine Finland (FI)
- Corresponding author
- Westermarck, Jukka
- Imanishi, Susumu Y.
- ORCID
- Venue
- Scientific Reports
- Published
- 2015-08-17
- Volume
- 5
- Issue
- 1
- Pages
- 13099-13099
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4642524
- OpenAlex
- W2412770710
- Cited by
- 61
- References
- 74
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 4 · 2023: 6 · 2022: 3 · 2021: 4 · 2020: 5 · 2019: 4 · 2018: 10 · 2017: 9 · 2016: 4 · 2015: 2
- FWCI
- 3.72
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UvA-DARE (University of Amsterdam) (acceptedVersion, cc-by)
- Työväentutkimus Vuosikirja (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Suomen Lääketieteen Säätiö
- Academy of Finland (269 862, 272 437, 252572)
- Turun Yliopistosäätiö
- Topics
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- 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
- Keywords
- Ras signaling, CIP2A, protein phosphatase 2A, phosphoproteomics, label-free quantification, phosphopeptide enrichment, KRAS mutation, oncogenic Ras
- MeSH terms
- Autoantigens, Chromatography, High Pressure Liquid, HeLa Cells, Humans, Membrane Proteins, Neoplasms, Phosphopeptides, Phosphorylation, ROC Curve, Titanium, Signal Transduction, Cluster Analysis, ras Proteins, Area Under Curve, RNA Interference, RNA, Small Interfering, Intracellular Signaling Peptides and Proteins, Cell Proliferation, Kaplan-Meier Estimate, Tandem Mass Spectrometry, Protein Phosphatase 2
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 ›
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