The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Ultradeep Human Phosphoproteome Reveals a Distinct Regulatory Nature of Tyr and Ser/Thr-Based Signaling
Open accessAbstract
Regulatory protein phosphorylation controls normal and pathophysiological signaling in eukaryotic cells. Despite great advances in mass-spectrometry-based proteomics, the extent, localization, and site-specific stoichiometry of this posttranslational modification (PTM) are unknown. Here, we develop a stringent experimental and computational workflow, capable of mapping more than 50,000 distinct phosphorylated peptides in a single human cancer cell line. We detected more than three-quarters of cellular proteins as phosphoproteins and determined very high stoichiometries in mitosis or growth factor signaling by label-free quantitation. The proportion of phospho-Tyr drastically decreases as coverage of the phosphoproteome increases, whereas Ser/Thr sites saturate only for technical reasons. Tyrosine phosphorylation is maintained at especially low stoichiometric levels in the absence of specific signaling events. Unexpectedly, it is enriched on higher-abundance proteins, and this correlates with the substrate KM values of tyrosine kinases. Our data suggest that P-Tyr should be considered a functionally separate PTM of eukaryotic proteomes.
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.
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
Cox, J., & Mann, M. (2008) · Nature Biotechnology · doi:10.1038/nbt.1511 · Cited by 14,855
Self-citationUniversal sample preparation method for proteome analysis
Wiśniewski, J. R., Zougman, A., Nagaraj, N., & Mann, M. (2009) · Nature Methods · doi:10.1038/nmeth.1322 · Cited by 8,352
Self-citationMichalski, A., Damoc, E., Hauschild, J.-P., Lange, O., Wieghaus, A., Makarov, A., Nagaraj, N., Cox, J., Mann, M., & Horning, S. (2011) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m111.011015 · Cited by 832
Self-citationWiśniewski, J. R., Zougman, A., & Mann, M. (2009) · Journal of Proteome Research · doi:10.1021/pr900748n · Cited by 545
Self-citationAnalysis of High Accuracy, Quantitative Proteomics Data in the MaxQB Database
Schaab, C., Geiger, T., Stoehr, G., Cox, J., & Mann, M. (2012) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m111.014068 · Cited by 164
Self-citation
Cited by
The Perseus computational platform for comprehensive analysis of (prote)omics data
Tyanova, S., Temu, T., Sinitcyn, P., Carlson, A., Hein, M. Y., Geiger, T., Mann, M., & Cox, J. (2016) · Nature Methods · doi:10.1038/nmeth.3901 · Cited by 8,803
Self-citationMass-spectrometric exploration of proteome structure and function
Aebersold, R., & Mann, M. (2016) · Nature · doi:10.1038/nature19949 · Cited by 2,334
Self-citationPhosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases
Steger, M., Tonelli, F., Ito, G., Davies, P., Trost, M., Vetter, M., Wachter, S., Lorentzen, E., Duddy, G., Wilson, S., et al. (2016) · eLife · doi:10.7554/elife.12813 · Cited by 1,042
Self-citationBassani-Sternberg, M., Bräunlein, E., Klar, R., Engleitner, T., Sinitcyn, P., Audehm, S., Straub, M., Weber, J., Slotta-Huspenina, J., Specht, K., et al. (2016) · Nature Communications · doi:10.1038/ncomms13404 · Cited by 693
Self-citationArendt, T., Stieler, J. T., & Holzer, M. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.08.018 · Cited by 609
The functional landscape of the human phosphoproteome
Ochoa, D., Jarnuczak, A. F., Viéitez, C., Gehre, M., Soucheray, M., Mateus, A., Kleefeldt, A. A., Hill, A., Garcia-Alonso, L., Stein, F., et al. (2020) · Nature Biotechnology · doi:10.1038/s41587-019-0344-3 · Cited by 491
Phosphoproteomics in the Age of Rapid and Deep Proteome Profiling
Riley, N. M., & Coon, J. J. (2016) · Analytical Chemistry · doi:10.1021/acs.analchem.5b04123 · Cited by 265
Protein Serine/Threonine Phosphatases: Keys to Unlocking Regulators and Substrates
Brautigan, D. L., & Shenolikar, S. (2018) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-062917-012332 · Cited by 191
Multi-omic Profiling Reveals Dynamics of the Phased Progression of Pluripotency
Yang, P., Humphrey, S. J., Cinghu, S., Pathania, R., Oldfield, A. J., Kumar, D., Perera, D., Yang, J. Y. H., James, D. E., Mann, M., et al. (2019) · Cell Systems · doi:10.1016/j.cels.2019.03.012 · Cited by 146
Self-citationSystems‐wide analysis of BCR signalosomes and downstream phosphorylation and ubiquitylation
Satpathy, S., Wagner, S. A., Beli, P., Gupta, R., Kristiansen, T. A., Malinova, D., Francavilla, C., Tolar, P., Bishop, G. A., Hostager, B. S., et al. (2015) · Molecular Systems Biology · doi:10.15252/msb.20145880 · Cited by 124
Inverso, D., Shi, J., Lee, K. H., Jakab, M., Ben-Moshe, S., Kulkarni, S. R., Schneider, M., Wang, G., Komeili, M., Vélez, P. A., et al. (2021) · Developmental Cell · doi:10.1016/j.devcel.2021.05.001 · Cited by 114
PICALM and Alzheimer’s Disease: An Update and Perspectives
Ando, K., Nagaraj, S., Küçükali, F., de Fisenne, M.-A., Kosa, A.-C., Doeraene, E., Lopez Gutierrez, L., Brion, J.-P., & Leroy, K. (2022) · Cells · doi:10.3390/cells11243994 · Cited by 104
Towards comprehensive and quantitative proteomics for diagnosis and therapy of human disease
Cifani, P., & Kentsis, A. (2017) · PROTEOMICS · doi:10.1002/pmic.201600079 · Cited by 101
Fast and deep phosphoproteome analysis with the Orbitrap Astral mass spectrometer
(2024) · doi:10.1038/s41467-024-51274-0 · Cited by 83
Kauko, 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
“S2) was restricted only to a fraction of observed phosphopeptides, our results are in line with previous reports of global bimodal distribution between dephosphorylated and phosphorylated peptides (1, 42).”
BackgroundResultSolleder, M., Guillaume, P., Racle, J., Michaux, J., Pak, H.-S., Müller, M., Coukos, G., Bassani-Sternberg, M., & Gfeller, D. (2020) · Molecular & Cellular Proteomics · doi:10.1074/mcp.tir119.001641 · Cited by 68
A framework for ultra-low-input spatial tissue proteomics
Makhmut, A., Qin, D., Fritzsche, S., Nimo, J., König, J., & Coscia, F. (2023) · Cell Systems · doi:10.1016/j.cels.2023.10.003 · Cited by 67
Kauko, O., Laajala, T. D., Jumppanen, M., Hintsanen, P., Suni, V., Haapaniemi, P., Corthals, G., Aittokallio, T., Westermarck, J., & Imanishi, S. Y. (2015) · Scientific Reports · doi:10.1038/srep13099 · Cited by 61
Ludwig, K. R., Sun, L., Zhu, G., Dovichi, N. J., & Hummon, A. B. (2015) · Analytical Chemistry · doi:10.1021/acs.analchem.5b02457 · Cited by 56
Clinical protein science in translational medicine targeting malignant melanoma
Gil, J., Betancourt, L. H., Pla, I., Sanchez, A., Appelqvist, R., Miliotis, T., Kuras, M., Oskolas, H., Kim, Y., Horvath, Z., et al. (2019) · Cell Biology and Toxicology · doi:10.1007/s10565-019-09468-6 · Cited by 45
Chen, B., Hwang, L., Ochowicz, W., Lin, Z., Guardado-Alvarez, T. M., Cai, W., Xiu, L., Dani, K., Colah, C., Jin, S., et al. (2017) · Chemical Science · doi:10.1039/c6sc05435h · Cited by 43
RIF1 acts in DNA repair through phosphopeptide recognition of 53BP1
Setiaputra, D., Escribano-Díaz, C., Reinert, J. K., Sadana, P., Zong, D., Callen, E., Sifri, C., Seebacher, J., Nussenzweig, A., Thomä, N. H., et al. (2022) · Molecular Cell · doi:10.1016/j.molcel.2022.01.025 · Cited by 43
Chen, D., Ludwig, K. R., Krokhin, O. V., Spicer, V., Yang, Z., Shen, X., Hummon, A. B., & Sun, L. (2019) · Analytical Chemistry · doi:10.1021/acs.analchem.8b04770 · Cited by 34
The Inner Nuclear Membrane Protein Nemp1 Is a New Type of RanGTP-Binding Protein in Eukaryotes
Shibano, T., Mamada, H., Hakuno, F., Takahashi, S.-I., & Taira, M. (2015) · PLOS ONE · doi:10.1371/journal.pone.0127271 · Cited by 27
CURTAIN—A unique web-based tool for exploration and sharing of MS-based proteomics data
Phung, T. K., Berndsen, K., Shastry, R., Phan, T. L. C. H. B., Muqit, M. M. K., Alessi, D. R., & Nirujogi, R. S. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2312676121 · Cited by 18
Hoermann, B., & Köhn, M. (2021) · Biochemical Society Transactions · doi:10.1042/bst20200175 · Cited by 14
Refsgaard, C. T., Barra, C., Peng, X., Ternette, N., & Nielsen, M. (2021) · ImmunoInformatics · doi:10.1016/j.immuno.2021.100005 · Cited by 12
The fitness cost of spurious phosphorylation
Bradley, D., Hogrebe, A., Dandage, R., Dubé, A. K., Leutert, M., Dionne, U., Chang, A., Villén, J., & Landry, C. R. (2024) · The EMBO Journal · doi:10.1038/s44318-024-00200-7 · Cited by 10
Deciphering the landscape of phosphorylated HLA-II ligands
Solleder, M., Racle, J., Guillaume, P., Coukos, G., Bassani-Sternberg, M., & Gfeller, D. (2022) · iScience · doi:10.1016/j.isci.2022.104215 · Cited by 9
Centromere protection requires strict mitotic inactivation of the Bloom syndrome helicase complex
Fernández-Casañas, M., Karanika, E., Aliyaskarova, U., Olukoga, T., Herbert, A. D., Oliver, A. W., Day, M., Crncec, A., & Chan, K.-L. (2025) · Nature Communications · doi:10.1038/s41467-025-62966-6 · Cited by 5
Dong, Q., Day, M., Saito, Y., Parker, E., Watts, L. P., Kanemaki, M. T., Oliver, A. W., Pearl, L. H., Hiraga, S.-I., & Donaldson, A. D. (2025) · Nature Communications · doi:10.1038/s41467-025-60817-y · Cited by 4
Woodard, J., Liu, Z., Chegini, A. M., Tian, J., Bhowmick, R., Pennathur, S., Mashaghi, A., Brender, J. R., & Chandrasekaran, S. (2025) · Cell Reports Methods · doi:10.1016/j.crmeth.2025.101169 · Cited by 3
A ubiquitination-mediated degradation system to target 14-3-3-binding phosphoproteins
Li, Z., Huang, X., Li, M., Chen, Y. E., Wang, Z., & Liu, L. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e16318 · Cited by 2
Centromere protection requires strict mitotic inactivation of the Bloom syndrome helicase complex
(2024) · doi:10.1101/2024.05.21.595148 · Cited by 2
Centromere protection requires strict mitotic inactivation of the Bloom syndrome helicase complex
Chan, K.-L., Fernández-Casañas, M., Karanika, E., Olukoga, T., Herbert, A., Aliyaskarova, U., & Day, M. (2024) · doi:10.21203/rs.3.rs-4420374/v1
Metadata
- Authors
- Sharma, K., D’Souza, R. C. J., Tyanova, S., Schaab, C., Wiśniewski, J. R., Cox, J., & Mann, M.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2014-09
- Volume
- 8
- Issue
- 5
- Pages
- 1583-1594
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W1996310767
- Cited by
- 969
- References
- 5
- FWCI
- 35.51
- Type
- journal article
- Language
- en
- Open access
- gold
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
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
