Quantitative cell proteomic atlas: Pathway-scale targeted mass spectrometry for high-resolution functional profiling of cell signaling Journal Article


Authors: Cifani, P.; Kentsis, A.
Article Title: Quantitative cell proteomic atlas: Pathway-scale targeted mass spectrometry for high-resolution functional profiling of cell signaling
Abstract: In spite of extensive studies of cellular signaling, many fundamental processes such as pathway integration, cross-talk, and feedback remain poorly understood. To enable integrated and quantitative measurements of cellular biochemical activities, we have developed the Quantitative Cell Proteomics Atlas (QCPA). QCPA consists of panels of targeted mass spectrometry assays to determine the abundance and stoichiometry of regulatory post-translational modifications of sentinel proteins from most known physiologic and pathogenic signaling pathways in human cells. QCPA currently profiles 1 »913 peptides from 469 effectors of cell surface signaling, apoptosis, stress response, gene expression, quiescence, and proliferation. For each protein, QCPA includes triplets of isotopically labeled peptides covering known post-translational regulatory sites to determine their stoichiometries and unmodified protein regions to measure total protein abundance. The QCPA framework incorporates analytes to control for technical variability of sample preparation and mass spectrometric analysis, including TrypQuant, a synthetic substrate for accurate quantification of proteolysis efficiency for proteins containing chemically modified residues. The ability to precisely and accurately quantify most known signaling pathways should enable improved chemoproteomic approaches for the comprehensive analysis of cell signaling and clinical proteomics of diagnostic specimens. QCPA is openly available at https://qcpa.mskcc.org. © 2022 American Chemical Society. All rights reserved.
Keywords: signal transduction; human cell; mass spectrometry; proteome; metabolism; gene expression; protein degradation; peptide; phosphorylation; proteomics; protein processing; protein processing, post-translational; peptides; tandem mass spectrometry; drug metabolism; cellular stress response; liquid chromatography; biochemistry; arginine; stoichiometry; electrospray; procedures; post-translational modification; chromatography; open access; solid phase extraction; physiological stress; cancer; humans; human; article; cell biologist; flight; biochemical regulation; ptm stoichiometry; targeted mass spectrometry; ammonium formate
Journal Title: Journal of Proteome Research
Volume: 21
Issue: 10
ISSN: 1535-3893
Publisher: American Chemical Society  
Date Published: 2022-10-07
Start Page: 2535
End Page: 2544
Language: English
DOI: 10.1021/acs.jproteome.2c00223
PUBMED: 36154077
PROVIDER: scopus
PMCID: PMC10494574
DOI/URL:
Notes: Article -- Export Date: 1 November 2022 -- Source: Scopus
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MSK Authors
  1. Alex   Kentsis
    103 Kentsis
  2. Paolo   Cifani
    32 Cifani