Ultradeep Human Phosphoproteome Reveals a Distinct Regulatory Nature of Tyr and Ser/Thr-Based Signaling

Ultradeep Human Phosphoproteome Reveals a Distinct Regulatory Nature of Tyr and Ser/Thr-Based Signaling

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Regulatory protein phosphorylation controls normal and pathophysiological signaling in eukaryotic cells.Despite great advances in mass-spectrometry-based proteomics, the extent, localization, Black French Cut Mid Rise Relaxed Short 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 Custom Made Halters of eukaryotic proteomes.