Mass spectrometry-based proteomics: Qualitative identification to activity-based protein profiling

Wiley Interdisciplinary Reviews: Systems Biology and Medicine

Volumn 4, Issue 2, 2012, Pages 141-162

  Cardoza, Job D ^a,b   Parikh, Jignesh R ^a,c   Ficarro, Scott B ^a,b   Marto, Jarrod A ^a,b  

^a DANA FARBER CANCER INSTITUTE   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c BOSTON UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGY; CLICK CHEMISTRY; COLLISIONALLY ACTIVATED DISSOCIATION; ELECTRON TRANSPORT; FRAGMENTATION REACTION; HUMAN; HYDROPHILIC INTERACTION CHROMATOGRAPHY; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; PREDICTION; PROTEIN ANALYSIS; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; PROTEOMICS; REVIEW; SIGNAL TRANSDUCTION;

CHROMATOGRAPHY, HIGH PRESSURE LIQUID; HUMANS; PHOSPHOPEPTIDES; PROTEIN INTERACTION MAPS; PROTEINS; PROTEOME; PROTEOMICS; TANDEM MASS SPECTROMETRY;

EID: 84857093197     PISSN: 19395094     EISSN: 1939005X     Source Type: Journal    
DOI: 10.1002/wsbm.166     Document Type: Review

References (175)

1. Weston AD, Hood L. Systems biology, proteomics, and the future of health care: toward predictive, preventative, and personalized medicine. J Proteome Res 2004, 3:179-196.
2. Schwartz JC, Senko MW, Syka JE. A two-dimensional quadrupole ion trap mass spectrometer. J Am Soc Mass Spectrom 2002, 13:659-669.
3. March RE. An introduction to quadrupole ion trap mass spectrometry. J Mass Spectrom 1997, 32: 351-369.
4. Makarov A, Denisov E, Kholomeev A, Balschun W, Lange O, Strupat K, Horning S. Performance evaluation of a hybrid linear ion trap/orbitrap mass spectrometer. Anal Chem 2006, 78:2113-2120.
5. Yates JR, Cociorva D, Liao L, Zabrouskov V. Performance of a linear ion trap-orbitrap hybrid for peptide analysis. Anal Chem 2006, 78:493-500.
6. Syka JE, Marto JA, Bai DL, Horning S, Senko MW, Schwartz JC, Ueberheide B, Garcia B, Busby S, Muratore T, et al. Novel linear quadrupole ion trap/FT mass spectrometer: performance characterization and use in the comparative analysis of histone H3 post-translational modifications. J Proteome Res 2004, 3:621-626.
7. Karas M, Hillenkamp F. Laser desorption ionization of proteins with molecular masses exceeding 10, 000 daltons. Anal Chem 1988, 60:2299-2301.
8. Medzihradszky KF, Campbell JM, Baldwin MA, Falick AM, Juhasz P, Vestal ML, Burlingame AL. The characteristics of peptide collision-induced dissociation using a high-performance MALDI-TOF/TOF tandem mass spectrometer. Anal Chem 2000, 72: 552-558.
9. Laiko VV, Baldwin MA, Burlingame AL. Atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry. Anal Chem 2000, 72:652-657.
10. Karas M, Bachmann D, Bahr U, Hillenkamp F. Matrix-assisted ultraviolet laser desorption of non-volatile compounds. Int J Mass Spectrom Ion Proc 1987, 78: 53-68.
11. Zenobi R, Knochenmuss R. Ion formation in MALDI mass spectrometry. Mass Spectrom Rev 1998, 17:337-366.
12. Tanaka K, Waki H, Ido Y, Akita S, Yoshida Y, Yoshida T, Matsuo T. Protein and polymer analyses up to m/z 100 000 by laser ionization time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 1988, 2:151-153.
13. Fenn JB, Mann M, Meng CK, Wong SF, Whitehouse CM. Electrospray ionization for mass spectrometry of large biomolecules. Science 1989, 246: 64-71.
14. Morris HR, Paxton T, Dell A, Langhorne J, Berg M, Bordoli RS, Hoyes J, Bateman RH. High sensitivity collisionally-activated decomposition tandem mass spectrometry on a novel quadrupole/orthogonal-acceleration time-of-flight mass spectrometer. Rapid Commun Mass Spectrom 1996, 10:889-896.
15. Yamashita M, Fenn JB. Electrospray ion source. Another variation on the free-jet theme. J Phys Chem 1984, 88:4451-4459.
16. Yamashita M, Fenn JB. Negative ion production with the electrospray ion source. J Phys Chem 1984, 88:4671-4675.
17. He F, Emmett MR, Hakansson K, Hendrickson CL, Marshall AG. Theoretical and experimental prospects for protein identification based solely on accurate mass measurement. J Proteome Res 2004, 3:61-67.
18. Taylor, BN, International Bureau of Weights and Measures. The International System of Units (SI). NIST special publication. U.S. Dept. of Commerce, Technology Administration. For sale by the Supt. of Docs., U.S. G.P.O.: Gaithersburg, MD; Washington; 2001, viii, 68.
19. Todd JFJ. Recommendations for nomenclature and symbolism for mass spectroscopy (including an appendix of terms used in vacuum technology). (recommendations 1991). Pure Appl Chem 1991, 63: 1541-1566.
20. Mamyrin BA. Time-of-flight mass spectrometry (concepts, achievements, and prospects). Int J Mass Spectrom 2001, 206:251-266.
21. Grundwürmer JM, Bönisch M, Kinsel GR, Grotemeyer J, Schlag EW. High-resolution mass spectrometry in a linear time-of-flight mass spectrometer. Int J Mass Spectrom Ion Proc 1994, 131:139-148.
22. Bienvenut WV, Déon C, Pasquarello C, Campbell JM, Sanchez J-C. Vestal ML, Hochstrasser DF. Matrix-assisted laser desorption/ionization-tandem mass spectrometry with high resolution and sensitivity for identification and characterization of proteins. Proteomics 2002, 2:868-876.
23. Pelander A, Decker P, Baessmann C, Ojanperä I. Evaluation of a high resolving power time-of-flight mass spectrometer for drug analysis in terms of resolving power and acquisition rate. J Am Soc Mass Spectrom 2011, 22:379-385.
24. Pandhal J, Ow SY, Noirel J, Wright PC. Improving N-glycosylation efficiency in Escherichia coli using shotgun proteomics, metabolic network analysis, and selective reaction monitoring. Biotechnol Bioeng 2011, 108:902-912.
25. Gorshkov MV, Zubarev RA. On the accuracy of polypeptide masses measured in a linear ion trap. Rapid Commun Mass Spectrom 2005, 19:3755-3758.
26. Hu Q, Noll RJ, Li H, Makarov A, Hardman M, Graham Cooks R. The Orbitrap: a new mass spectrometer. J Mass Spectrom 2005, 40:430-443.
27. He F, Hendrickson CL, Marshall AG. Baseline mass resolution of peptide isobars: a record for molecular mass resolution. Anal Chem 2001, 73:647-650.
28. Zubarev RA, Håkansson P, Sundqvist B. Accuracy requirements for peptide characterization by monoisotopic molecular mass measurements. Anal Chem 1996, 68:4060-4063.
29. McLuckey SA, Van Berkel GJ, Glish GL, Huang EC, Henion JD. Ion spray liquid chromatography/ion trap mass spectrometry determination of biomolecules. Anal Chem 1991, 63:375-383.
30. Olsen JV, Macek B, Lange O, Makarov A, Horning S, Mann M. Higher-energy C-trap dissociation for peptide modification analysis. Nat Meth 2007, 4:709-712.
31. Hunt DF, Buko AM, Ballard JM, Shabanowitz J, Giordani AB. Sequence analysis of polypeptides by collision activated dissociation on a triple quadrupole mass spectrometer. Biomed Mass Spectrom (now incorporated into J Mass Spectrom) 1981, 8:397-408.
32. Syka JE, Coon JJ, Schroeder MJ, Shabanowitz J, Hunt DF. Peptide and protein sequence analysis by electron transfer dissociation mass spectrometry. Proc Natl Acad Sci U S A 2004, 101:9528-9533.
33. Mikesh LM, Ueberheide B, Chi A, Coon JJ, Syka JE, Shabanowitz J, Hunt DF. The utility of ETD mass spectrometry in proteomic analysis. Biochim Biophys Acta 2006, 1764:1811-1822.
34. McLafferty FW, Horn DM, Breuker K, Ge Y, Lewis MA, Cerda B, Zubarev RA, Carpenter BK. Electron capture dissociation of gaseous multiply charged ions by Fourier-transform ion cyclotron resonance. J Am Soc Mass Spectrom 2001, 12:245-249.
35. Zubarev RA, Kelleher NL, McLafferty FW. Electron capture dissociation of multiply charged protein cations. A nonergodic process. J Am Chem Soc 1998, 120:3265-3266.
36. Turecek F, McLafferty FW. Non-ergodic behavior in acetone-enol ion dissociations. J Am Chem Soc 1984, 106:2525-2528.
37. Perkins DN, Pappin DJ, Creasy DM, Cottrell JS. Probability-based protein identification by searching sequence databases using mass spectrometry data. Electrophoresis 1999, 20:3551-3567.
38. Ducret A, Van Oostveen I, Eng JK, Yates JR, 3rd, Aebersold R. High throughput protein characterization by automated reverse-phase chromatography/electrospray tandem mass spectrometry. Protein Sci 1998, 7:706-719.
39. Phenyx. Available from: (Accessed November 18, 2011).
40. Colinge J, Masselot A, Giron M, Dessingy T, Magnin J. OLAV: towards high-throughput tandem mass spectrometry data identification. Proteomics 2003, 3:1454-1463.
41. Craig R, Beavis RC. TANDEM: matching proteins with tandem mass spectra. Bioinformatics 2004, 20:1466-1467.
42. Sadygov RG, Cociorva D, Yates JR, 3rd. Large-scale database searching using tandem mass spectra: looking up the answer in the back of the book. Nat Methods 2004, 1:195-202.
43. Kapp E, Schütz F. Overview of Tandem Mass Spectrometry (MS/MS) database search algorithms. Curr Protoc Prot Sci 2001, Chapter 25 (Unit 25.2).
44. Balgley BM, Laudeman T, Yang L, Song T, Lee CS. Comparative evaluation of tandem MS search algorithms using a target-decoy search strategy. Mol Cell Proteomics 2007, 6:1599-1608.
45. Nesvizhskii AI, Keller A, Kolker E, Aebersold R. A statistical model for identifying proteins by tandem mass spectrometry. Anal Chem 2003, 75:4646-4658.
46. Nesvizhskii AI, Aebersold R. Interpretation of shotgun proteomic data: the protein inference problem. Mol Cell Proteomics 2005, 4:1419-1440.
47. Carr S. The need for guidelines in publication of peptide and protein identification data: working group on publication guidelines for peptide and protein identification data. Mol Cell Proteomics 2004, 3:531-533.
48. Mann M, Hendrickson RC, Pandey A. Analysis of proteins and proteomes by mass spectrometry. Annu Rev Biochem 2001, 70:437-473.
49. Palagi PM, Hernandez P, Walther D, Appel RD. Proteome informatics I: bioinformatics tools for processing experimental data. Proteomics 2006, 6:5435-5444.
50. Illustrations generated using ACD/Chemsketch Freeware. version 12.01, Toronto, ON, Canada: Advanced Chemistry Development, Inc; 2010. Available at: (Accessed February 9, 2011).
51. Roepstorff P, Fohlman J. Proposal for a common nomenclature for sequence ions in mass spectra of peptides. Biomed Mass Spectrom 1984, 11:601.
52. Johnson RS, Martin SA, Biemann K, Stults JT, Watson JT. Novel fragmentation process of peptides by collision-induced decomposition in a tandem mass spectrometer: differentiation of leucine and isoleucine. Anal Chem 1987, 59:2621-2625.
53. Schlosser A, Lehmann WD. Five-membered ring formation in unimolecular reactions of peptides: a key structural element controlling low-energy collision-induced dissociation of peptides. J Mass Spectrom 2000, 35:1382-1390.
54. Polce MJ, Ren D, Wesdemiotis C. Dissociation of the peptide bond in protonated peptides. J Mass Spectrom 2000, 35:1391-1398.
55. Griffiths WJ. The encyclopedia of mass spectrometry. In: Gross ML, Caprioli RM, eds. Biological Applications: Part A: Peptides and Proteins, Vol 2. Amsterdam; Boston: Elsevier; 2005, 71-74.
56. Chi A, Huttenhower C, Geer LY, Coon JJ, Syka JEP, Bai DL, Shabanowitz J, Burke DJ, Troyanskaya OG, Hunt DF. Analysis of phosphorylation sites on proteins from Saccharomyces cerevisiae by electron transfer dissociation (ETD) mass spectrometry. Proc Nat Acad Sci USA 2007, 104:2193-2198.
57. Olsen JV, Ong SE, Mann M. Trypsin cleaves exclusively C-terminal to arginine and lysine residues. Mol Cell Proteomics 2004, 3:608-614.
58. Mann M, Wilm M. Error-tolerant identification of peptides in sequence databases by peptide sequence tags. Anal Chem 1994, 66:4390-4399.
59. BLAST: Basic Local Alignment Search Tool, National Center for Biotechnology Information. Available at: (Accessed February 17, 2011).
60. Audia G, Wapstrab AH, Thibaulta C. The AME2003 atomic mass evaluation (II). Tables, graphs, and references. Nucl Phys A 2003, 729:337-676.
61. Wieser ME, Berglund M. Atomic weights of the elements 2007 (IUPAC Technical Report). Pure Appl Chem 2009, 81:2131-2156.
62. Caprioli RM, Gross ML, eds. The Encyclopedia of Mass Spectrometry, Volume 2: Biological Applications: Part A: Peptides and Proteins. Elsevier; 2005, 173-174.
63. Ong SE, Blagoev B, Kratchmarova I, Kristensen DB, Steen H, Pandey A, Mann M. Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol Cell Proteomics 2002, 1:376-386.
64. Mann M. Functional and quantitative proteomics using SILAC. Nat Rev Mol Cell Biol 2006, 7:952-958.
65. Gerber SA, Rush J, Stemman O, Kirschner MW, Gygi SP. Absolute quantification of proteins and phosphoproteins from cell lysates by tandem MS. Proc Natl Acad Sci U S A 2003, 100:6940-6945.
66. Gygi SP, Rist B, Gerber SA, Turecek F, Gelb MH, Aebersold R. Quantitative analysis of complex protein mixtures using isotope-coded affinity tags. Nat Biotechnol 1999, 17:994-999.
67. Gygi SP, Rist B, Griffin TJ, Eng J, Aebersold R. Proteome analysis of low-abundance proteins using multidimensional chromatography and isotope-coded affinity tags. J Proteome Res 2002, 1:47-54.
68. Ross PL, Huang YN, Marchese JN, Williamson B, Parker K, Hattan S, Khainovski N, Pillai S, Dey S, Daniels S, et al. Multiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagents. Mol Cell Proteomics 2004, 3:1154-1169.
69. Phanstiel D, Zhang Y, Marto JA, Coon JJ. Peptide and protein quantification using iTRAQ with electron transfer dissociation. J Am Soc Mass Spectrom 2008, 19:1255-1262.
70. Thompson A, Schafer J, Kuhn K, Kienle S, Schwarz J, Schmidt G, Neumann T, Johnstone R, Mohammed AK, Hamon C. Tandem mass tags: a novel quantification strategy for comparative analysis of complex protein mixtures by MS/MS. Anal Chem 2003, 75:1895-1904.
71. Dayon L, Hainard A, Licker V, Turck N, Kuhn K, Hochstrasser DF, Burkhard PR, Sanchez JC. Relative quantification of proteins in human cerebrospinal fluids by MS/MS using 6-plex isobaric tags. Anal Chem 2008, 80:2921-2931.
72. Wang W, Zhou H, Lin H, Roy S, Shaler TA, Hill LR, Norton S, Kumar P, Anderle M, Becker CH. Quantification of proteins and metabolites by mass spectrometry without isotopic labeling or spiked standards. Anal Chem 2003, 75:4818-4826.
73. Anderle M, Roy S, Lin H, Becker C, Joho K. Quantifying reproducibility for differential proteomics: noise analysis for protein liquid chromatography-mass spectrometry of human serum. Bioinformatics 2004, 20:3575-3582.
74. Bantscheff M, Schirle M, Sweetman G, Rick J, Kuster B. Quantitative mass spectrometry in proteomics: a critical review. Anal Bioanal Chem 2007, 389:1017-1031.
75. Breitwieser FP, Muller A, Dayon L, Kocher T, Hainard A, Pichler P, Schmidt-Erfurth U, Superti-Furga G, Sanchez JC, Mechtler K, et al. General statistical modeling of data from protein relative expression isobaric tags. J Proteome Res 2011, 10:2758-2766.
76. auf dem Keller U, Prudova A, Gioia M, Butler GS, Overall CM. A statistics-based platform for quantitative N-terminome analysis and identification of protease cleavage products. Mol Cell Proteomics 2010, 9:912-927.
77. Zhang Y, Askenazi M, Jiang J, Luckey CJ, Griffin JD, Marto JA. A robust error model for iTRAQ quantification reveals divergent signaling between oncogenic FLT3 mutants in acute myeloid leukemia. Mol Cell Proteomics 2010, 9:780-790.
78. Fenyo D, Qin J, Chait BT. Protein identification using mass spectrometric information. Electrophoresis 1998, 19:998-1005.
79. Gan CS, Chong PK, Pham TK, Wright PC. Technical, experimental, and biological variations in isobaric tags for relative and absolute quantitation (iTRAQ). J Proteome Res 2007, 6:821-827.
80. Boehm AM, Putz S, Altenhofer D, Sickmann A, Falk M. Precise protein quantification based on peptide quantification using iTRAQ. BMC Bioinform 2007, 8:214.
81. Oda Y, Nagasu T, Chait BT. Enrichment analysis of phosphorylated proteins as a tool for probing the phosphoproteome. Nat Biotechnol 2001, 19:379-382.
82. Goshe MB, Veenstra TD, Panisko EA, Conrads TP, Angell NH, Smith RD. Phosphoprotein isotope-coded affinity tags: application to the enrichment and identification of low-abundance phosphoproteins. Anal Chem 2002, 74:607-616.
83. McLachlin DT, Chait BT. Improved β-elimination-based affinity purification strategy for enrichment of phosphopeptides. Anal Chem 2003, 75:6826-6836.
84. Zhou H, Watts JD, Aebersold R. A systematic approach to the analysis of protein phosphorylation. Nat Biotechnol 2001, 19:375-378.
85. Tao WA, Wollscheid B, O'Brien R, Eng JK, Li XJ, Bodenmiller B, Watts JD, Hood L, Aebersold R. Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry. Nature Methods 2005, 2:591-598.
86. Nuwaysir LM, Stults JT. Electrospray ionization mass spectrometry of phosphopeptides isolated by on-line immobilized metal-ion affinity chromatography. J Am Soc Mass Spectrom 1993, 4:662-669.
87. Watts JD, Affolter M, Krebs DL, Wange RL, Samelson LE, Aebersold R. Identification by electrospray ionization mass spectrometry of the sites of tyrosine phosphorylation induced in activated Jurkat T cells on the protein tyrosine kinase ZAP-70. J Biol Chem 1994, 269:29520-29529.
88. Posewitz MC, Tempst P. Immobilized gallium(III) affinity chromatography of phosphopeptides. Anal Chem 1999, 71:2883-2892.
89. Ficarro SB, McCleland ML, Stukenberg PT, Burke DJ, Ross MM, Shabanowitz J, Hunt DF, White FM. Phosphoproteome analysis by mass spectrometry and its application to Saccharomyces cerevisiae. Nat Biotechnol 2002, 20:301-305.
90. Ficarro S, Chertihin O, Westbrook VA, White F, Jayes F, Kalab P, Marto JA, Shabanowitz J, Herr JC, Hunt DF. et al. Phosphoproteome analysis of capacitated human sperm. Evidence of tyrosine phosphorylation of a kinase-anchoring protein 3 and valosin-containing protein/p97 during capacitation. J Biol Chem 2003, 278:11579-11589.
91. Ndassa YM, Orsi C, Marto JA, Chen S, Ross MM. Improved immobilized metal affinity chromatography for large-scale phosphoproteomics applications. J Proteome Res 2006, 5:2789-2799.
92. Ficarro SB, Adelmant G, Tomar MN, Zhang Y, Cheng VJ, Marto JA. Magnetic bead processor for rapid evaluation and optimization of parameters for phosphopeptide enrichment. Anal Chem 2009, 81:4566-4575.
93. Pinkse MW, Uitto PM, Hilhorst MJ, Ooms B, Heck AJ. Selective isolation at the femtomole level of phosphopeptides from proteolytic digests using 2D-NanoLC-ESI-MS/MS and titanium oxide precolumns. Anal Chem 2004, 76:3935-3943.
94. Larsen MR, Thingholm TE, Jensen ON, Roepstorff P, Jorgensen TJ. Highly selective enrichment of phosphorylated peptides from peptide mixtures using titanium dioxide microcolumns. Mol Cell Proteomics 2005, 4:873-886.
95. Tsai CF, Wang YT, Chen YR, Lai CY, Lin PY, Pan KT, Chen JY, Khoo KH, Chen YJ. Immobilized metal affinity chromatography revisited: pH/acid control toward high selectivity in phosphoproteomics. J Proteome Res 2008, 7:4058-4069.
96. Sugiyama N, Masuda T, Shinoda K, Nakamura A, Tomita M, Ishihama Y. Phosphopeptide enrichment by aliphatic hydroxy acid-modified metal oxide chromatography for nano-LC-MS/MS in proteomics applications. Mol Cell Proteomics 2007, 6:1103-1109.
97. Kweon HK, Hakansson K. Selective zirconium dioxide-based enrichment of phosphorylated peptides for mass spectrometric analysis. Anal Chem 2006, 78:1743-1749.
98. 5): application to phosphoproteomics. Anal Chem 2008, 80:4606-4613.
99. Leitner A. Phosphopeptide enrichment using metal oxide affinity chromatography. Trac-Trends Anal Chem 2010, 29:177-185.
100. Hung CW, Kubler D, Lehmann WD. pI-based phosphopeptide enrichment combined with nanoESI-MS. Electrophoresis 2007, 28:2044-2052.
101. Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villen J, Li J, Cohn MA, Cantley LC, Gygi SP. Large-scale characterization of HeLa cell nuclear phosphoproteins. Proc Natl Acad Sci U S A 2004, 101:12130-12135.
102. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP. A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A 2008, 105:10762-10767.
103. Dai J, Wang LS, Wu YB, Sheng QH, Wu JR, Shieh CH, Zeng R. Fully automatic separation and identification of phosphopeptides by continuous pH-gradient anion exchange online coupled with reversed-phase liquid chromatography mass spectrometry. J Proteome Res 2009, 8:133-141.
104. Albuquerque CP, Smolka MB, Payne SH, Bafna V, Eng J, Zhou H. A multidimensional chromatography technology for in-depth phosphoproteome analysis. Mol Cell Proteomics 2008, 7:1389-1396.
105. McNulty DE, Annan RS. Hydrophilic interaction chromatography reduces the complexity of the phosphoproteome and improves global phosphopeptide isolation and detection. Mol Cell Proteomics 2008, 7:971-980.
106. Alpert AJ. Electrostatic repulsion hydrophilic interaction chromatography for isocratic separation of charged solutes and selective isolation of phosphopeptides. Anal Chem 2008, 80:62-76.
107. Zarei M, Sprenger A, Metzger F, Gretzmeier C, Dengjel J. Comparison of ERLIC-TiO(2), HILIC-TiO(2), and SCX-TiO(2) for Global Phosphoproteomics Approaches. J Proteome Res 2011, 10:3474-3483.
108. Hunter T. The Croonian Lecture 1997. The phosphorylation of proteins on tyrosine: its role in cell growth and disease. Phil Trans Biol Sci 1998, 353:583-605.
109. Hunter T, Sefton BM. Transforming gene product of Rous sarcoma virus phosphorylates tyrosine. Proc Natl Acad Sci U S A 1980, 77:1311-1315.
110. Salomon AR, Ficarro SB, Brill LM, Brinker A, Phung QT, Ericson C, Sauer K, Brock A, Horn DM, Schultz PG. Profiling of tyrosine phosphorylation pathways in human cells using mass spectrometry. Proc Natl Acad Sci 2003, 100:443-448.
111. Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ. Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nature Biotechnol 2005, 23:94-101.
112. Zhang Y, Wolf-Yadlin A, Ross PL, Pappin DJ, Rush J, Lauffenburger DA, White FM. Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules. Mol Cell Proteomics 2005, 4:1240-1250.
113. Annan RS, Huddleston MJ, Verma R, Deshaies RJ, Carr SA. A multidimensional electrospray MS-based approach to phosphopeptide mapping. Anal Chem 2001, 73:393-404.
114. Schlosser A, Pipkorn R, Bossemeyer D, Lehmann WD. Analysis of protein phosphorylation by a combination of elastase digestion and neutral loss tandem mass spectrometry. Anal Chem 2000, 73:170-176.
115. Song C, Ye M, Han G, Jiang X, Wang F, Yu Z, Chen R, Zou H. Reversed-phase-reversed-phase liquid chromatography approach with high orthogonality for multidimensional separation of phosphopeptides. Anal Chem 2010, 82:53-56.
116. Ficarro SB, Zhang Y, Carrasco-Alfonso MJ, Garg B, Adelmant G, Webber JT, Luckey CJ, Marto JA. Online nanoflow multi-dimensional fractionation for high efficiency phosphopeptide analysis. Mol Cell Proteomics 2011, 10:O111.011064.
117. Payne SH, Yau M, Smolka MB, Tanner S, Zhou HL, Bafna V. Phosphorylation-specific MS/MS scoring for rapid and accurate phosphoproteome analysis. J Proteome Res 2008, 7:3373-3381.
118. Beausoleil SA, Villen J, Gerber SA, Rush J, Gygi SP. A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nature Biotechnol 2006, 24:1285-1292.
119. Savitski MM, Lemeer S, Boesche M, Lang M, Mathieson T, Bantscheff M, Kuster B. Confident phosphorylation site localization using the mascot delta score. Mol Cell Proteomics 2011, 10:M110003830.
120. Choe L, D'Ascenzo M, Relkin NR, Pappin D, Ross P, Williamson B, Guertin S, Pribil P, Lee KH. 8-plex quantitation of changes in cerebrospinal fluid protein expression in subjects undergoing intravenous immunoglobulin treatment for Alzheimer's disease. Proteomics 2007, 7:3651-3660.
121. Phanstiel D, Unwin R, McAlister GC, Coon JJ. Peptide quantification using 8-plex isobaric tags and electron transfer dissociation tandem mass spectrometry. Anal Chem 2009, 81:1693-1698.
122. Wolf-Yadlin A, Kumar N, Zhang Y, Hautaniemi S, Zaman M, Kim HD, Grantcharova V, Lauffenburger DA, White FM. Effects of HER2 overexpression on cell signaling networks governing proliferation and migration. Mol Syst Biol 2006, 54.
123. Tang LY, Deng N, Wang LS, Dai J, Wang ZL, Jiang XS, Li SJ, Li L, Sheng QH, Wu DQ. Quantitative phosphoproteome profiling of Wnt3a-mediated signaling network: indicating the involvement of ribonucleoside-diphosphate reductase M2 subunit phosphorylation at residue serine 20 in canonical Wnt signal transduction. Mol Cell Proteomics 2007, 6:1952-1967.
124. Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, et al. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 2000, 25:25-29.
125. Kanehisa M, Goto S, Hattori M, Aoki-Kinoshita KF, Itoh M, Kawashima S, Katayama T, Araki M, Hirakawa M. From genomics to chemical genomics: new developments in KEGG. Nucleic Acids Res 2006, 34:D354-D357.
126. BioCarta Pathways. Available at: (Accessed November 18, 2011).
127. Stark C, Breitkreutz BJ, Reguly T, Boucher L, Breitkreutz A, Tyers M. BioGRID: a general repository for interaction datasets. Nucleic Acids Res 2006, 34:D535-D539.
128. Keshava Prasad TS, Goel R, Kandasamy K, Keerthikumar S, Kumar S, Mathivanan S, Telikicherla D, Raju R, Shafreen B, Venugopal A, et al. Human protein reference database-2009 update. Nucleic Acids Res 2009, 37:D767-D772.
129. Zhou F, Cardoza JD, Ficarro SB, Adelmant GO, Lazaro JB, Marto JA. Online nanoflow RP-RP-MS reveals dynamics of multicomponent Ku complex in response to DNA damage. J Proteome Res 2010, 9:6242-6255.
130. Ficarro SB, Zhang Y, Lu Y, Moghimi AR, Askenazi M, Hyatt E, Smith ED, Boyer L, Schlaeger TM, Luckey CJ, et al. Improved electrospray ionization efficiency compensates for diminished chromatographic resolution and enables proteomics analysis of tyrosine signaling in embryonic stem cells. Anal Chem 2009, 81:3440-3447.
131. Askenazi M, Li S, Singh S, Marto JA. Pathway Palette: a rich internet application for peptide-, protein- and network-oriented analysis of MS data. Proteomics 2010, 10:1880-1885.
132. Dennis G, Jr. Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki RA. DAVID: database for annotation, visualization, and integrated discovery. Genome Biol 2003, 4:P3.
133. Chang JT, Nevins JR. GATHER: a systems approach to interpreting genomic signatures. Bioinformatics 2006, 22:2926-2933.
134. Dumont JE, Pecasse F, Maenhaut C. Crosstalk and specificity in signalling. Are we crosstalking ourselves into general confusion? Cell Signal 2001, 13:457-463.
135. Force T, Woulfe K, Koch WJ, Kerkela R. Molecular scaffolds regulate bidirectional crosstalk between Wnt and classical seven-transmembrane-domain receptor signaling pathways. Sci STKE 2007, 2007:pe41.
136. Javelaud D, Mauviel A. Crosstalk mechanisms between the mitogen-activated protein kinase pathways and Smad signaling downstream of TGF-β: implications for carcinogenesis. Oncogene 2005, 24:5742-5750.
137. Matozaki T, Nakanishi H, Takai Y. Small G-protein networks: their crosstalk and signal cascades. Cell Signal 2000, 12:515-524.
138. Breitkreutz A, Choi H, Sharom JR, Boucher L, Neduva V, Larsen B, Lin ZY, Breitkreutz BJ, Stark C, Liu G, et al. A global protein kinase and phosphatase interaction network in yeast. Science 2010, 328:1043-1046.
139. Overgaard AJ, Thingholm TE, Larsen MR, Tarnow L, Rossing P, McGuire JN, Pociot F. Quantitative iTRAQ-based proteomic identification of candidate biomarkers for diabetic nephropathy in plasma of type 1 diabetic patients. Clin Proteomics 2010, 6:105-114.
140. Huang SS, Fraenkel E. Integrating proteomic, transcriptional, and interactome data reveals hidden components of signaling and regulatory networks. Sci Signal 2009, 2:ra40.
141. Kumar N, Wolf-Yadlin A, White FM, Lauffenburger DA. Modeling HER2 effects on cell behavior from mass spectrometry phosphotyrosine data. PLoS Comput Biol 2007, 3:e4.
142. Woolf PJ, Prudhomme W, Daheron L, Daley GQ, Lauffenburger DA. Bayesian analysis of signaling networks governing embryonic stem cell fate decisions. Bioinformatics 2005, 21:741-753.
143. Van Hoof D, Munoz J, Braam SR, Pinkse MW, Linding R, Heck AJ, Mummery CL, Krijgsveld J. Phosphorylation dynamics during early differentiation of human embryonic stem cells. Cell Stem Cell 2009, 5:214-226.
144. Linding R, Jensen LJ, Ostheimer GJ, van Vugt MA, Jorgensen C, Miron IM, Diella F, Colwill K, Taylor L, Elder K, et al. Systematic discovery of in vivo phosphorylation networks. Cell 2007, 129:1415-1426.
145. Szklarczyk D, Franceschini A, Kuhn M, Simonovic M, Roth A, Minguez P, Doerks T, Stark M, Muller J, Bork P, et al. The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res 2011, 39: D561-D568.
146. Blom N, Sicheritz-Ponten T, Gupta R, Gammeltoft S, Brunak S. Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence. Proteomics 2004, 4:1633-1649.
147. Obenauer JC, Cantley LC, Yaffe MB. Scansite 2.0: Proteome-wide prediction of cell signaling interactions using short sequence motifs. Nucleic Acids Res 2003, 31:3635-3641.
148. Washburn MP, Wolters D, Yates JR. Large-scale analysis of the yeast proteome by multidimensional protein identification technology. Nature Biotechnol 2001, 19:242.
149. Stennicke HR, Salvesen GS. Caspases-controlling intracellular signals by protease zymogen activation. Biochim Biophys Acta 2000, 1477:299-306.
150. Adams JA. Activation loop phosphorylation and catalysis in protein kinases: is there functional evidence for the autoinhibitor model? Biochemistry 2003, 42: 601-607.
151. Patricelli MP, Szardenings AK, Liyanage M, Nomanbhoy TK, Wu M, Weissig H, Aban A, Chun D, Tanner S, Kozarich JW. Functional interrogation of the kinome using nucleotide acyl phosphates. Biochemistry 2006, 46:350-358.
152. Liu Y, Patricelli MP, Cravatt BF. Activity-based protein profiling: the serine hydrolases. Proc Natl Acad Sci U S A 1999, 96:14694-14699.
153. Greenbaum D, Medzihradszky KF, Burlingame A, Bogyo M. Epoxide electrophiles as activity-dependent cysteine protease profiling and discovery tools. Chem Biol 2000, 7:569-581.
154. Shreder KR, Liu YS, Nomanhboy T, Fuller SR, Wong MS, Gai WZ, Wu JY, Leventhal PS, Lill JR, Corral S. Design and synthesis of AX7574: A microcystin-derived, fluorescent probe for serine/threonine phosphatases. Bioconjugate Chem 2004, 15:790-798.
155. Vocadlo DJ, Bertozzi CR. A strategy for functional proteomic analysis of glycosidase activity from cell lysates. Angew Chem Int Ed; 2004, 43:5338-5342.
156. Cravatt BF, Wright AT, Kozarich JW. Activity-based protein profiling: from enzyme chemistry. Annu Rev Biochem 2008, 77:383-414.
157. Speers AE, Cravatt BF. Profiling enzyme activities in vivo using click chemistry methods. Chem Biol 2004, 11:535-546.
158. Kolb HC, Finn MG, Sharpless KB. Click chemistry: diverse chemical function from a few good reactions. Angew Chem Int Ed; 2001, 40:2004-2021.
159. Huisgen R. 1, 3-Dipolar cycloadditions. Past and future. Angew Chem Int Ed; 1963, 2:565-598.
160. Rostovtsev VV, Green LG, Fokin VV, Sharpless KB. A stepwise huisgen cycloaddition process: copper(I)-catalyzed regioselective "ligation" of azides and terminal alkynes. Angew Chem Int Ed 2002, 41: 2596-2599.
161. Tornoe CW, Christensen C, Meldal M. Peptidotriazoles on solid phase: 1, 2, 3-triazoles by regiospecific copper(I)-catalyzed 1, 3-dipolar cycloadditions of terminal alkynes to azides. J Organ Chem 2002, 67:3057-3064.
162. Chan TR, Hilgraf R, Sharpless KB, Fokin VV. Polytriazoles as copper(I)-stabilizing ligands in catalysis. Organ Lett 2004, 6:2853-2855.
163. Baskin JM, Prescher JA, Laughlin ST, Agard NJ, Chang PV, Miller IA, Lo A, Codelli JA, Bertozzi CR. Copper-free click chemistry for dynamic in vivo imaging. Proc Natl Acad Sci 2007, 104:16793-16797.
164. Chang PV, Prescher JA, Sletten EM, Baskin JM, Miller IA, Agard NJ, Lo A, Bertozzi CR. Copper-free click chemistry in living animals. Proc Natl Acad Sci U S A 2010, 107:1821-1826.
165. Laughlin ST, Baskin JM, Amacher SL, Bertozzi CR. In vivo imaging of membrane-associated glycans in developing zebrafish. Science 2008, 320:664-667.
166. Weerapana E, Speers AE, Cravatt BF. Tandem orthogonal proteolysis-activity-based protein profiling (TOP-ABPP)-a general method for mapping sites of probe modification in proteomes. Nat Protocols 2007, 2:1414-1425.
167. Nomura DK, Dix MM, Cravatt BF. Activity-based protein profiling for biochemical pathway discovery in cancer. Nature Rev Cancer 2010, 10:630-638.
168. Shields DJ, Niessen S, Murphy EA, Mielgo A, Desgrosellier JS, Lau SKM, Barnes LA, Lesperance J, Bouvet M, Tarin D, et al. RBBP9: a tumor-associated serine hydrolase activity required for pancreatic neoplasia. Proc Natl Acad Sci U S A 2010, 107: 2189-2194.
169. Jessani N, Liu YS, Humphrey M, Cravatt BF. Enzyme activity profiles of the secreted and membrane proteome that depict cancer cell invasiveness. Proc Natl Acad Sci U S A 2002, 99:10335-10340.
170. Jessani N, Humphrey M, McDonald WH, Niessen S, Masuda K, Gangadharan B, Yates JR, Mueller BM, Cravatt BF. Carcinoma and stromal enzyme activity profiles associated with breast tumor growth in vivo. Proc Natl Acad Sci U S A 2004, 101:13756-13761.
171. Nomura DK, Long JZ, Niessen S, Hoover HS, Ng SW, Cravatt BF. Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis. Cell 2010, 140:49-61.
172. Boja E, Hiltke T, Rivers R, Kinsinger C, Rahbar A, Mesri M, Rodriguez H. Evolution of clinical proteomics and its role in medicine. J Proteome Res 2010, 10:66-84.
173. Sturgeon C. Perspectives in clinical proteomics conference: translating clinical proteomics into clinical practice. Expert Rev Proteomics 2010, 7:469-471.
174. Apweiler R, Aslanidis C, Deufel T, Gerstner A, Hansen J, Hochstrasser D, Kellner R, Kubicek M, Lottspeich F, Maser E, et al. Approaching clinical proteomics: current state and future fields of application in fluid proteomics. Clin Chem Lab Med 2009, 47:724-744.
175. Addona TA, Abbatiello SE, Schilling B, Skates SJ, Mani DR, Bunk DM, Spiegelman CH, Zimmerman LJ, Ham AJ, Keshishian H, et al. Multi-site assessment of the precision and reproducibility of multiple reaction monitoring-based measurements of proteins in plasma. Nat Biotechnol 2009, 27:633-641.