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Molecular & Cellular Proteomics
Article . 2011 . Peer-reviewed
License: CC BY
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Molecular & Cellular Proteomics
Article
License: CC BY
Data sources: UnpayWall
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Correct Interpretation of Comprehensive Phosphorylation Dynamics Requires Normalization by Protein Expression Changes

Authors: Ronghu, Wu; Noah, Dephoure; Wilhelm, Haas; Edward L, Huttlin; Bo, Zhai; Mathew E, Sowa; Steven P, Gygi;

Correct Interpretation of Comprehensive Phosphorylation Dynamics Requires Normalization by Protein Expression Changes

Abstract

The interpretation of quantitative phosphoproteomics studies is complicated because each differential phosphorylation event integrates both changes in protein expression and phosphorylation. Here we investigated this phenomenon by performing parallel comparisons of protein expression and phosphorylation in S. cerevisiae. In each of two experiments comparing yeast mutants bearing deletions in FUS3 or STE7 with their wild-type counterparts, we quantified over 4100 proteins, including all members of the yeast mating pathway. We also identified 12,499 unique phosphorylation sites in this work. We demonstrate the critical importance of controlling the protein-level false-discovery rate and provide a novel method to assess the accuracy of protein false-discovery rate estimates. For the first time, 96% of nonredundant phosphopeptide ratios could be calibrated by protein levels, allowing truly differential phosphorylation to be distinguished from altered protein expression. This revealed a starkly different view, with 25% of seemingly differential phosphopeptides now attributed to changes in protein expression. Combined protein expression and phosphorylation surveys uncovered both independent and concerted changes in protein expression and phosphorylation, while highlighting the partially redundant role of a second MAPK (Kss1) in the mating pathway.

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Keywords

Mitogen-Activated Protein Kinase Kinases, Saccharomyces cerevisiae Proteins, Proteome, MAP Kinase Signaling System, Gene Expression, Saccharomyces cerevisiae, Phosphoproteins, Gene Knockout Techniques, Calibration, Reproduction, Asexual, Amino Acid Sequence, Mitogen-Activated Protein Kinases, Phosphorylation, Protein Kinases, Protein Processing, Post-Translational

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
157
Top 1%
Top 10%
Top 1%
gold