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Cited by 969

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 access
Sharma, Kirti, D’Souza, Rochelle C.J., Tyanova, Stefka, Schaab, Christoph, Wiśniewski, Jacek R., Cox, Jürgen, Mann, Matthias·2014·Cell Reports

Abstract

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.

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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

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Sharma, K., D’Souza, R. C. J., Tyanova, S., Schaab, C., Wiśniewski, J. R., Cox, J., & Mann, M. (2014). Ultradeep Human Phosphoproteome Reveals a Distinct Regulatory Nature of Tyr and Ser/Thr-Based Signaling. Cell Reports. https://doi.org/10.1016/j.celrep.2014.07.036

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