REVIEW

Mass spectrometry-based phosphoproteomics in cancer research

  • Xiao-Shan YUE ,
  • Amanda B. HUMMON
Expand
  • Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA

Received date: 04 Sep 2012

Accepted date: 16 Oct 2012

Published date: 01 Dec 2012

Copyright

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg

Abstract

Phosphorylation is one of the most common post translational modifications (PTM), participating in a large number of processes to regulate cellular functions. Phosphorylation is also one of the key factors in the origin and development of cancer. The rapid development of mass spectrometric-based phosphoproteomic technologies has made it possible for high-throughput identification and quantification of phosphorylation events. In this review, we provide a general introduction and summary of the achievements made in mass spectrometry based phosphoproteomic research, including the approaches for phosphopeptide identification and quantification, as well as instrumentation and data interpretation methods. We also review some discoveries in cancer research made possible by phosphoproteomic analysis technologies.

Cite this article

Xiao-Shan YUE , Amanda B. HUMMON . Mass spectrometry-based phosphoproteomics in cancer research[J]. Frontiers in Biology, 2012 , 7(6) : 566 -586 . DOI: 10.1007/s11515-012-2022-4

Acknowledgments

The authors wish to thank the Walther Cancer Foundation and the Notre Dame Harper Cancer Research Institute for postdoctoral funding for XY. Also, the authors appreciate many helpful discussions with the staff of the Notre Dame Mass Spectrometry and Proteomics Facility.
1
Ali N A, Molloy M P (2011). Quantitative phosphoproteomics of transforming growth factor-β signaling in colon cancer cells. Proteomics, 11(16): 3390–3401

DOI PMID

2
Alpert A J (1990). Hydrophilic-interaction chromatography for the separation of peptides, nucleic acids and other polar compounds. J Chromatogr A, 499: 177–196

DOI PMID

3
Andersson L (1991). Recognition of phosphate groups by immobilized aluminium (III) ions. J Chromatogr A, 539(2): 327–334

DOI

4
Andersson L, Porath J (1986). Isolation of phosphoproteins by immobilized metal (Fe3+) affinity chromatography. Anal Biochem, 154(1): 250–254

DOI PMID

5
Anguenot R, Yelle S, Nguyen-Quoc B (1999). Purification of tomato sucrose synthase phosphorylated isoforms by Fe(III)-immobilized metal affinity chromatography. Arch Biochem Biophys, 365(1): 163–169

DOI PMID

6
Aryal U K, Olson D J, Ross A R (2008). Optimization of immobilized gallium (III) ion affinity chromatography for selective binding and recovery of phosphopeptides from protein digests. J Biomol Tech, 19(5): 296–310

PMID

7
Beausoleil S A, Jedrychowski M, Schwartz D, Elias J E, Villén J, Li J, Cohn M A, Cantley L C, Gygi S P (2004). Large-scale characterization of HeLa cell nuclear phosphoproteins. Proc Natl Acad Sci USA, 101(33): 12130–12135

DOI PMID

8
Beausoleil S A, Villén J, Gerber S A, Rush J, Gygi S P (2006). A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nat Biotechnol, 24(10): 1285–1292

DOI PMID

9
Beli P, Lukashchuk N, Wagner S A, Weinert B T, Olsen J V, Baskcomb L, Mann M, Jackson S P, Choudhary C (2012). Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response. Mol Cell, 46(2): 212–225

DOI PMID

10
Bensimon A, Schmidt A, Ziv Y, Elkon R, Wang S Y, Chen D J, Aebersold R, Shiloh Y (2010). ATM-dependent and-independent dynamics of the nuclear phosphoproteome after DNA damage. Sci Signal, 3(151): rs3

DOI PMID

11
Biarc J, Chalkley R J, Burlingame A L, Bradshaw R A (2011). Receptor tyrosine kinase signaling—a proteomic perspective. Adv Enzyme Regul, 51(1): 293–305

DOI PMID

12
Bodenmiller B, Mueller L N, Mueller M, Domon B, Aebersold R (2007). Reproducible isolation of distinct, overlapping segments of the phosphoproteome. Nat Methods, 4(3): 231–237

DOI PMID

13
Boersema P J, Mohammed S, Heck A J (2009). Phosphopeptide fragmentation and analysis by mass spectrometry. J Mass Spectrom, 44(6): 861–878

DOI PMID

14
Bogdanov B, Smith R D (2005). Proteomics by FTICR mass spectrometry: top down and bottom up. Mass Spectrom Rev, 24(2): 168–200

DOI PMID

15
Boja E S, Phillips D, French S A, Harris R A, Balaban R S (2009). Quantitative mitochondrial phosphoproteomics using iTRAQ on an LTQ-Orbitrap with high energy collision dissociation. J Proteome Res, 8(10): 4665–4675

DOI PMID

16
Breuker K, Jin M, Han X, Jiang H, McLafferty F W (2008). Top-down identification and characterization of biomolecules by mass spectrometry. J Am Soc Mass Spectrom, 19(8): 1045–1053

DOI PMID

17
Bridges S M, Magee G B, Wang N, Williams W P, Burgess S C, Nanduri B (2007). ProtQuant: a tool for the label-free quantification of MudPIT proteomics data. BMC Bioinformatics, 8(Suppl 7): S24

DOI PMID

18
Buhrman D L, Price P I, Rudewicz P J (1996). Quantitation of SR 27417 in human plasma using electrospray liquid chromatography-tandem mass spectrometry: a study of ion suppression. J Am Soc Mass Spectrom, 7(11): 1099–1105

DOI

19
Cantin G T, Shock T R, Park S K, Madhani H D, Yates J R 3rd (2007). Optimizing TiO2-based phosphopeptide enrichment for automated multidimensional liquid chromatography coupled to tandem mass spectrometry. Anal Chem, 79(12): 4666–4673

DOI PMID

20
Carr S A, Huddleston M J, Annan R S (1996). Selective detection and sequencing of phosphopeptides at the femtomole level by mass spectrometry. Anal Biochem, 239(2): 180–192

DOI PMID

21
Chen J, Gallo K A (2012). MLK3 regulates paxillin phosphorylation in chemokine-mediated breast cancer cell migration and invasion to drive metastasis. Cancer Res, 72(16): 4130–4140

DOI PMID

22
Chen X, Smith L M, Bradbury E M (2000). Site-specific mass tagging with stable isotopes in proteins for accurate and efficient protein identification. Anal Chem, 72(6): 1134–1143

DOI PMID

23
Chen Y Y, Dasari S, Ma Z Q, Vega-Montoto L J, Li M, Tabb D L (2012). Refining comparative proteomics by spectral counting to account for shared peptides and multiple search engines. Anal Bioanal Chem, 404(4): 1115–1125

DOI PMID

24
Cheng G, Zhang J L, Liu Y L, Sun D H, Ni J Z (2011). Synthesis of novel Fe3O4@SiO2@CeO2 microspheres with mesoporous shell for phosphopeptide capturing and labeling. Chem Commun (Camb), 47(20): 5732–5734

DOI PMID

25
Christensen E, Evans K R, Ménard C, Pintilie M, Bristow R G (2008). Practical approaches to proteomic biomarkers within prostate cancer radiotherapy trials. Cancer Metastasis Rev, 27(3): 375–385

DOI PMID

26
Ciccia A, Elledge S J (2010). The DNA damage response: making it safe to play with knives. Mol Cell, 40(2): 179–204

DOI PMID

27
Cohen P (2000). The regulation of protein function by multisite phosphorylation—a 25 year update. Trends Biochem Sci, 25(12): 596–601

DOI PMID

28
Cox J, Mann M (2008). MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat Biotechnol, 26(12): 1367–1372

DOI PMID

29
Cox J, Matic I, Hilger M, Nagaraj N, Selbach M, Olsen J V, Mann M (2009). A practical guide to the MaxQuant computational platform for SILAC-based quantitative proteomics. Nat Protoc, 4(5): 698–705

DOI PMID

30
Cox J, Neuhauser N, Michalski A, Scheltema R A, Olsen J V, Mann M (2011). Andromeda: a peptide search engine integrated into the MaxQuant environment. J Proteome Res, 10(4): 1794–1805

DOI PMID

31
Craig R, Beavis R C (2003). A method for reducing the time required to match protein sequences with tandem mass spectra. Rapid Commun Mass Spectrom, 17(20): 2310–2316

DOI PMID

32
Craig R, Beavis R C (2004). TANDEM: matching proteins with tandem mass spectra. Bioinformatics, 20(9): 1466–1467

DOI PMID

33
Cuccurullo M, Schlosser G, Cacace G, Malorni L, Pocsfalvi G (2007). Identification of phosphoproteins and determination of phosphorylation sites by zirconium dioxide enrichment and SELDI-MS/MS. J Mass Spectrom, 42(8): 1069–1078

DOI PMID

34
Cui W, Rohrs H W, Gross M L (2011). Top-down mass spectrometry: recent developments, applications and perspectives. Analyst (Lond), 136(19): 3854–3864

DOI PMID

35
Dai J, Jin W H, Sheng Q H, Shieh C H, Wu J R, Zeng R (2007). Protein phosphorylation and expression profiling by Yin-yang multidimensional liquid chromatography (Yin-yang MDLC) mass spectrometry. J Proteome Res, 6(1): 250–262

DOI PMID

36
Dayon L, Pasquarello C, Hoogland C, Sanchez J C, Scherl A (2010). Combining low- and high-energy tandem mass spectra for optimized peptide quantification with isobaric tags. J Proteomics, 73(4): 769–777

DOI PMID

37
Deeb S J, D’Souza R C, Cox J, Schmidt-Supprian Ms Mann M (2012). Super-STLAC allows classification of diffuse large B-cell lymphoma subtypes by their protein expression profiles. Mol Cell Proteomics, 11(5): 77–89<DOI OutputMedium="All"/><PubMed OutputMedium="All"/>

38
Dephoure N, Gygi S P (2011). A solid phase extraction-based platform for rapid phosphoproteomic analysis. Methods, 54(4): 379–386

DOI PMID

38
Dephoure N, Gygi S P (2011). A solid phase extraction-based platform for rapid phosphoproteomic analysis. Methods, 54(4): 379–386

DOI PMID

39
Elias J E, Gygi S P (2007). Target-decoy search strategy for increased confidence in large-scale protein identifications by mass spectrometry. Nat Methods, 4(3): 207–214

DOI PMID

40
Eng J K, Mccormack A L, Yates J R (1994). An approach to correlate tandem mass-spectral data of peptides with amino-acid-sequences in a protein database. J Am Soc Mass Spectrom, 5(11): 976–989

DOI

41
Evans C, Noirel J, Ow S Y, Salim M, Pereira-Medrano A G, Couto N, Pandhal J, Smith D, Pham T K, Karunakaran E, Zou X, Biggs C A, Wright P C (2012). An insight into iTRAQ: where do we stand now? Anal Bioanal Chem, 404(4): 1011–1027

DOI PMID

42
Eyrich B, Sickmann A, Zahedi R P (2011). Catch me if you can: mass spectrometry-based phosphoproteomics and quantification strategies. Proteomics, 11(4): 554–570

DOI PMID

43
Feng S, Pan C, Jiang X, Xu S, Zhou H, Ye M, Zou H (2007a). Fe3+ immobilized metal affinity chromatography with silica monolithic capillary column for phosphoproteome analysis. Proteomics, 7(3): 351–360

DOI PMID

44
Feng S, Ye M, Zhou H, Jiang X, Jiang X, Zou H, Gong B (2007b). Immobilized zirconium ion affinity chromatography for specific enrichment of phosphopeptides in phosphoproteome analysis. Mol Cell Proteomics, 6(9): 1656–1665

DOI PMID

45
Ficarro S B, McCleland M L, Stukenberg P T, Burke D J, Ross M M, Shabanowitz J, Hunt D F, White F M (2002). Phosphoproteome analysis by mass spectrometry and its application to Saccharomyces cerevisiae. Nat Biotechnol, 20(3): 301–305

DOI PMID

46
Frese C K, Altelaar A F, Hennrich M L, Nolting D, Zeller M, Griep-Raming J, Heck A J, Mohammed S (2011). Improved peptide identification by targeted fragmentation using CID, HCD and ETD on an LTQ-Orbitrap Velos. J Proteome Res, 10(5): 2377–2388

DOI PMID

47
Furic L, Rong L, Larsson O, Koumakpayi I H, Yoshida K, Brueschke A, Petroulakis E, Robichaud N, Pollak M, Gaboury L A, Pandolfi P P, Saad F, Sonenberg N (2010). eIF4E phosphorylation promotes tumorigenesis and is associated with prostate cancer progression. Proc Natl Acad Sci USA, 107(32): 14134–14139

DOI PMID

48
Garrett T J, Merves M, Yost R A (2011). Characterization of protonated phospholipids as fragile ions in quadrupole ion trap mass spectrometry. Int J Mass Spectrom, 308(2–3): 299–306

DOI PMID

49
Geiger T, Madden S F, Gallagher W M, Cox J, Mann M (2012). Proteomic portrait of human breast cancer progression identifies novel prognostic markers. Cancer Res, 72(9): 2428–2439

DOI PMID

50
Gerber S A, Rush J, Stemman O, Kirschner M W, Gygi S P (2003). Absolute quantification of proteins and phosphoproteins from cell lysates by tandem MS. Proc Natl Acad Sci USA, 100(12): 6940–6945

DOI PMID

51
Good D M, Wirtala M, McAlister G C, Coon J J (2007). Performance characteristics of electron transfer dissociation mass spectrometry. Mol Cell Proteomics, 6(11): 1942–1951

DOI PMID

52
Goshe M B (2006). Characterizing phosphoproteins and phosphoproteomes using mass spectrometry. Brief Funct Genomics Proteomics, 4(4): 363–376

DOI PMID

53
Grimsrud P A, Swaney D L, Wenger C D, Beauchene N A, Coon J J (2010). Phosphoproteomics for the masses. ACS Chem Biol, 5(1): 105–119

DOI PMID

54
Guha U, Chaerkady R, Marimuthu A, Patterson A S, Kashyap M K, Harsha H C, Sato M, Bader J S, Lash A E, Minna J D, Pandey A, Varmus H E (2008). Comparisons of tyrosine phosphorylated proteins in cells expressing lung cancer-specific alleles of EGFR and KRAS. Proc Natl Acad Sci USA, 105(37): 14112–14117

DOI PMID

55
Gygi S P, Rist B, Gerber S A, Turecek F, Gelb M H, Aebersold R (1999). Quantitative analysis of complex protein mixtures using isotope-coded affinity tags. Nat Biotechnol, 17(10): 994–999

DOI PMID

56
Han G, Ye M, Zhou H, Jiang X, Feng S, Jiang X, Tian R, Wan D, Zou H, Gu J (2008a). Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography. Proteomics, 8(7): 1346–1361

DOI PMID

57
Han G, Ye M, Zou H (2008b). Development of phosphopeptide enrichment techniques for phosphoproteome analysis. Analyst (Lond), 133(9): 1128–1138

DOI PMID

58
Hanahan D, Weinberg R A (2000). The hallmarks of cancer. Cell, 100(1): 57–70

DOI PMID

59
Hanahan D, Weinberg R A (2011). Hallmarks of cancer: the next generation. Cell, 144(5): 646–674

DOI PMID

60
Hao P, Zhang H, Sze S K (2011). Application of electrostatic repulsion hydrophilic interaction chromatography to the characterization of proteome, glycoproteome, and phosphoproteome using nano LC-MS/MS. Methods Mol Biol, 790: 305–318

DOI PMID

61
Hennrich M L, Groenewold V, Kops G J, Heck A J, Mohammed S (2011). Improving depth in phosphoproteomics by using a strong cation exchange-weak anion exchange-reversed phase multidimensional separation approach. Anal Chem, 83(18): 7137–7143

DOI PMID

62
Hoeijmakers J H (2009). DNA damage, aging, and cancer. N Engl J Med, 361(15): 1475–1485

DOI PMID

63
Holmberg C I, Tran S E, Eriksson J E, Sistonen L (2002). Multisite phosphorylation provides sophisticated regulation of transcription factors. Trends Biochem Sci, 27(12): 619–627

DOI PMID

64
Hornbeck P V, Kornhauser J M, Tkachev S, Zhang B, Skrzypek E, Murray B, Latham V, Sullivan M (2012). PhosphoSitePlus: a comprehensive resource for investigating the structure and function of experimentally determined post-translational modifications in man and mouse. Nucleic Acids Res, 40(D1 Database issue): D261–D270

DOI PMID

65
Hsiao H H, Urlaub H (2010). Pseudo-neutral-loss scan for selective detection of phosphopeptides and N-glycopeptides using liquid chromatography coupled with a hybrid linear ion-trap/orbitrap mass spectrometer. Proteomics, 10(21): 3916–3921

DOI PMID

66
Huang P H (2012). Phosphoproteomic studies of receptor tyrosine kinases: future perspectives. Mol Biosyst, 8(4): 1100–1107

DOI PMID

67
Hung K E, Yu K H (2010). Proteomic approaches to cancer biomarkers. Gastroenterology, 138(1): 46–51, e1

DOI PMID

68
Hunt D F, Yates J R 3rd, Shabanowitz J, Winston S, Hauer C R (1986). Protein sequencing by tandem mass spectrometry. Proc Natl Acad Sci USA, 83(17): 6233–6237

DOI PMID

69
Huttlin E L, Jedrychowski M P, Elias J E, Goswami T, Rad R, Beausoleil S A, Villén J, Haas W, Sowa M E, Gygi S P (2010). A tissue-specific atlas of mouse protein phosphorylation and expression. Cell, 143(7): 1174–1189

DOI PMID

70
Ikeguchi Y, Nakamura H (1997). Determination of organic phosphates by column-switching high performance anion-exchange chromatography using on-line preconcentration on titania. Anal Sci, 13(3): 479–485

71
Imamura H, Wakabayashi M, Ishihama Y (2012). Analytical strategies for shotgun phosphoproteomics: Status and prospects. Semin Cell Dev Biol, Available online <day>5</day><month>June</month>2012, http://dx.doi.org/10.1016/j.semcdb.2012.05.007

72
Imanishi S Y, Kochin V, Eriksson J E (2007). Optimization of phosphopeptide elution conditions in immobilized Fe(III) affinity chromatography. Proteomics, 7(2): 174–176

DOI PMID

73
Indovina P, Marcelli E, Pentimalli F, Tanganelli P, Tarro G, Giordano A (2012). Mass spectrometry-based proteomics: The road to lung cancer biomarker discovery. Mass Spectrom Rev: n/a doi: 10.1002/mas.21355

PMID

74
Ishihama Y, Sato T, Tabata T, Miyamoto N, Sagane K, Nagasu T, Oda Y (2005). Quantitative mouse brain proteomics using culture-derived isotope tags as internal standards. Nat Biotechnol, 23(5): 617–621

DOI PMID

75
Jackson S P, Bartek J (2009). The DNA-damage response in human biology and disease. Nature, 461(7267): 1071–1078

DOI PMID

76
Jadaliha M, Lee H J, Pakzad M, Fathi A, Jeong S K, Cho S Y, Baharvand H, Paik Y K, Salekdeh G H (2012). Quantitative proteomic analysis of human embryonic stem cell differentiation by 8-plex iTRAQ labelling. PLoS ONE, 7(6): e38532

DOI PMID

77
Jedrychowski M P, Huttlin E L, Haas W, Sowa M E, Rad R, Gygi S P (2011). Evaluation of HCD- and CID-type fragmentation within their respective detection platforms for murine phosphoproteomics. Mol Cell Proteomics, 10(12):M111.009910

78
Jiang X, Han G, Feng S, Jiang X, Ye M, Yao X, Zou H (2008). Automatic validation of phosphopeptide identifications by the MS2/MS3 target-decoy search strategy. J Proteome Res, 7(4): 1640–1649

DOI PMID

79
Jiang X, Ye M, Cheng K, Zou H (2010). ArMone: a software suite specially designed for processing and analysis of phosphoproteome data. J Proteome Res, 9(5): 2743–2751

DOI PMID

80
Jin W H, Dai J, Zhou H, Xia Q C, Zou H F, Zeng R (2004). Phosphoproteome analysis of mouse liver using immobilized metal affinity purification and linear ion trap mass spectrometry. Rapid Commun Mass Spectrom, 18(18): 2169–2176

DOI PMID

81
Jones A M, Nuhse T S (2011). Phosphoproteomics using iTRAQ. Methods Mol Biol, 779: 287–302

DOI PMID

82
Jorgensen T J (2009). Enhancing radiosensitivity: targeting the DNA repair pathways. Cancer Biol Ther, 8(8): 665–670

DOI PMID

83
Jun H J, Johnson H, Bronson R T, de Feraudy S, White F, Charest A (2012). The oncogenic lung cancer fusion kinase CD74-ROS activates a novel invasiveness pathway through E-Syt1 phosphorylation. Cancer Res, 72(15): 3764–3774

DOI PMID

84
Kanshin E, Michnick S, Thibault P (2012). Sample preparation and analytical strategies for large-scale phosphoproteomics experiments. Semin Cell Dev Biol, Available online <day>5</day><month>June</month>2012, http://dx.doi.org/10.1016/j.semcdb.2012.05.005

85
Kapp E, Schutz F (2007). Overview of tandem mass spectrometry (MS/MS) database search algorithms. Curr Protoc Protein Sci, Chapter 25: t22–t25

86
Kito K, Ito T (2008). Mass spectrometry-based approaches toward absolute quantitative proteomics. Curr Genomics, 9(4): 263–274

DOI PMID

87
Kok M, Holm-Wigerup C, Hauptmann M, Michalides R, Stål O, Linn S, Landberg G (2009). Estrogen receptor-alpha phosphorylation at serine-118 and tamoxifen response in breast cancer. J Natl Cancer Inst, 101(24): 1725–1729

DOI PMID

88
Kong F, Nicole White C, Xiao X, Feng Y, Xu C, He D, Zhang Z, Yu Y (2006). Using proteomic approaches to identify new biomarkers for detection and monitoring of ovarian cancer. Gynecol Oncol, 100(2): 247–253

DOI PMID

89
Kosako H, Nagano K (2011). Quantitative phosphoproteomics strategies for understanding protein kinase-mediated signal transduction pathways. Expert Rev Proteomics, 8(1): 81–94

DOI PMID

90
Kozak K R, Amneus M W, Pusey S M, Su F, Luong M N, Luong S A, Reddy S T, Farias-Eisner R (2003). Identification of biomarkers for ovarian cancer using strong anion-exchange ProteinChips: potential use in diagnosis and prognosis. Proc Natl Acad Sci USA, 100(21): 12343–12348

DOI PMID

91
Kristensen D B, Imamura K, Miyamoto Y, Yoshizato K (2000). Mass spectrometric approaches for the characterization of proteins on a hybrid quadrupole time-of-flight (Q-TOF) mass spectrometer. Electrophoresis, 21(2): 430–439

DOI PMID

92
Krüger M, Moser M, Ussar S, Thievessen I, Luber C A, Forner F, Schmidt S, Zanivan S, Fässler R, Mann M (2008). SILAC mouse for quantitative proteomics uncovers kindlin-3 as an essential factor for red blood cell function. Cell, 134(2): 353–364

DOI PMID

93
Kuroda I, Shintani Y, Motokawa M, Abe S, Furuno M (2004). Phosphopeptide-selective column-switching RP-HPLC with a titania precolumn. Anal Sci, 20(9): 1313–1319

DOI PMID

94
Larger P J, Breda M, Fraier D, Hughes H, James C A (2005). Ion-suppression effects in liquid chromatography-tandem mass spectrometry due to a formulation agent, a case study in drug discovery bioanalysis. J Pharm Biomed Anal, 39(1-2): 206–216

DOI PMID

95
Larsen M R, Thingholm T E, Jensen O N, Roepstorff P, Jørgensen T J (2005). Highly selective enrichment of phosphorylated peptides from peptide mixtures using titanium dioxide microcolumns. Mol Cell Proteomics, 4(7): 873–886

DOI PMID

96
Lee D H, Goodarzi A A, Adelmant G O, Pan Y, Jeggo P A, Marto J A, Chowdhury D (2012). Phosphoproteomic analysis reveals that PP4 dephosphorylates KAP-1 impacting the DNA damage response. EMBO J, 31(10): 2403–2415

DOI PMID

97
Lee J, Xu Y, Chen Y, Sprung R, Kim S C, Xie S, Zhao Y (2007). Mitochondrial phosphoproteome revealed by an improved IMAC method and MS/MS/MS. Mol Cell Proteomics, 6(4): 669–676

DOI PMID

98
Lehmann W D, Krüger R, Salek M, Hung C W, Wolschin F, Weckwerth W (2007). Neutral loss-based phosphopeptide recognition: a collection of caveats. J Proteome Res, 6(7): 2866–2873

DOI PMID

99
Lemeer S, Kunold E, Klaeger S, Raabe M, Towers M W, Claudes E, Arrey T N, Strupat K, Urlaub H, Kuster B (2012). Phosphorylation site localization in peptides by MALDI MS/MS and the Mascot Delta Score. Anal Bioanal Chem, 402(1): 249–260

DOI PMID

100
Li Q R, Ning Z B, Tang J S, Nie S, Zeng R (2009). Effect of peptide-to-TiO2 beads ratio on phosphopeptide enrichment selectivity. J Proteome Res, 8(11): 5375–5381

DOI PMID

101
Li S, Dass C (1999). Iron(III)-immobilized metal ion affinity chromatography and mass spectrometry for the purification and characterization of synthetic phosphopeptides. Anal Biochem, 270(1): 9–14

DOI PMID

102
Li Y, Xu X, Qi D, Deng C, Yang P, Zhang X (2008). Novel Fe3O4@TiO2 core-shell microspheres for selective enrichment of phosphopeptides in phosphoproteome analysis. J Proteome Res, 7(6): 2526–2538

DOI PMID

103
Liang X, Fonnum G, Hajivandi M, Stene T, Kjus N H, Ragnhildstveit E, Amshey J W, Predki P, Pope R M (2007). Quantitative comparison of IMAC and TiO2 surfaces used in the study of regulated, dynamic protein phosphorylation. J Am Soc Mass Spectrom, 18(11): 1932–1944

DOI PMID

104
Lim K B, Kassel D B (2006). Phosphopeptides enrichment using on-line two-dimensional strong cation exchange followed by reversed-phase liquid chromatography/mass spectrometry. Anal Biochem, 354(2): 213–219

DOI PMID

105
Lim Y P (2005). Mining the tumor phosphoproteome for cancer markers. Clin Cancer Res, 11(9): 3163–3169

DOI PMID

106
Lin L, Hutzen B, Zuo M, Ball S, Deangelis S, Foust E, Pandit B, Ihnat M A, Shenoy S S, Kulp S, Li P K, Li C, Fuchs J, Lin J (2010). Novel STAT3 phosphorylation inhibitors exhibit potent growth-suppressive activity in pancreatic and breast cancer cells. Cancer Res, 70(6): 2445–2454

DOI PMID

107
Liu H, Stupak J, Zheng J, Keller B O, Brix B J, Fliegel L, Li L (2004). Open tubular immobilized metal ion affinity chromatography combined with MALDI MS and MS/MS for identification of protein phosphorylation sites. Anal Chem, 76(14): 4223–4232

DOI PMID

108
Lo T, Tsai C F, Shih Y R, Wang Y T, Lu S C, Sung T Y, Hsu W L, Chen Y J, Lee O K (2012). Phosphoproteomic analysis of human mesenchymal stromal cells during osteogenic differentiation. J Proteome Res, 11(2): 586–598

DOI PMID

109
Lu M, Faull K F, Whitelegge J P, He J, Shen D, Saxton R E, Chang H R (2007). Proteomics and mass spectrometry for cancer biomarker discovery. Biomark Insights, 2: 347–360

PMID

110
Macek B, Mann M, Olsen J V (2009). Global and site-specific quantitative phosphoproteomics: principles and applications. Annu Rev Pharmacol Toxicol, 49(1): 199–221

DOI PMID

111
Machida M, Kosako H, Shirakabe K, Kobayashi M, Ushiyama M, Inagawa J, Hirano J, Nakano T, Bando Y, Nishida E, Hattori S (2007). Purification of phosphoproteins by immobilized metal affinity chromatography and its application to phosphoproteome analysis. FEBS J, 274(6): 1576–1587

DOI PMID

112
Makarov A, Denisov E, Kholomeev A, Balschun W, Lange O, Strupat K, Horning S (2006a). Performance evaluation of a hybrid linear ion trap/orbitrap mass spectrometer. Anal Chem, 78(7): 2113–2120

DOI PMID

113
Makarov A, Denisov E, Lange O, Horning S (2006b). Dynamic range of mass accuracy in LTQ Orbitrap hybrid mass spectrometer. J Am Soc Mass Spectrom, 17(7): 977–982

DOI PMID

114
Mallet C R, Lu Z, Mazzeo J R (2004). A study of ion suppression effects in electrospray ionization from mobile phase additives and solid-phase extracts. Rapid Commun Mass Spectrom, 18(1): 49–58

DOI PMID

115
Mant C T, Litowski J R, Hodges R S (1998). Hydrophilic interaction/cation-exchange chromatography for separation of amphipathic α-helical peptides. J Chromatogr A, 816(1): 65–78

DOI PMID

116
Mayya V, Han D K (2009). Phosphoproteomics by mass spectrometry: insights, implications, applications and limitations. Expert Rev Proteomics, 6(6): 605–618

DOI PMID

117
Mazanek M, Mituloviae G, Herzog F, Stingl C, Hutchins J R, Peters J M, Mechtler K (2007). Titanium dioxide as a chemo-affinity solid phase in offline phosphopeptide chromatography prior to HPLC-MS/MS analysis. Nat Protoc, 2(5): 1059–1069

DOI PMID

118
Mazanek M, Roitinger E, Hudecz O, Hutchins J R, Hegemann B, Mitulović G, Taus T, Stingl C, Peters J M, Mechtler K (2010). A new acid mix enhances phosphopeptide enrichment on titanium- and zirconium dioxide for mapping of phosphorylation sites on protein complexes. J Chromatogr B Analyt Technol Biomed Life Sci, 878(5–6): 515–524

DOI PMID

119
Mazsaroff I, Rounds M A, Regnier F E (1987). Facile preparation of a non-porous strong anion-exchange column for proteins. J Chromatogr A, 411: 452–455

DOI PMID

120
McAlister G C, Berggren W T, Griep-Raming J, Horning S, Makarov A, Phanstiel D, Stafford G, Swaney D L, Syka J E, Zabrouskov V, Coon J J (2008). A proteomics grade electron transfer dissociation-enabled hybrid linear ion trap-orbitrap mass spectrometer. J Proteome Res, 7(8): 3127–3136

DOI PMID

121
McClatchy D B, Liao L, Park S K, Venable J D, Yates J R (2007). Quantification of the synaptosomal proteome of the rat cerebellum during post-natal development. Genome Res, 17(9): 1378–1388

DOI PMID

122
McClatchy D B, Liao L, Park S K, Xu T, Lu B, Yates Iii J R (2011). Differential proteomic analysis of mammalian tissues using SILAM. PLoS ONE, 6(1): e16039

DOI PMID

123
McNulty D E, Annan R S (2008). Hydrophilic interaction chromatography reduces the complexity of the phosphoproteome and improves global phosphopeptide isolation and detection. Mol Cell Proteomics, 7(5): 971–980

DOI PMID

124
McNulty D E, Annan R S (2009). Hydrophilic interaction chromatography for fractionation and enrichment of the phosphoproteome. Methods Mol Biol, 527: 93–105

DOI PMID

125
Mertins P, Udeshi N D, Clauser K R, Mani D R, Patel J, Ong S E, Jaffe J D, Carr S A (2012). iTRAQ labeling is superior to mTRAQ for quantitative global proteomics and phosphoproteomics. Mol Cell Proteomics, 11(6):M111.014423

126
Metodiev M, Alldridge L (2008). Phosphoproteomics: A possible route to novel biomarkers of breast cancer. Proteomics Clin Appl, 2(2): 181–194

DOI PMID

127
Michalski A, Damoc E, Hauschild J P, Lange O, Wieghaus A, Makarov A, Nagaraj N, Cox J, Mann M, Horning S (2011). Mass spectrometry-based proteomics using Q Exactive, a high-performance benchtop quadrupole Orbitrap mass spectrometer. Mol Cell Proteomics, 10(9):M111.011015

128
Monetti M, Nagaraj N, Sharma K, Mann M (2011). Large-scale phosphosite quantification in tissues by a spike-in SILAC method. Nat Methods, 8(8): 655–658

DOI PMID

129
Morandell S, Stasyk T, Skvortsov S, Ascher S, Huber L A (2008). Quantitative proteomics and phosphoproteomics reveal novel insights into complexity and dynamics of the EGFR signaling network. Proteomics, 8(21): 4383–4401

DOI PMID

130
Mortensen P, Gouw J W, Olsen J V, Ong S E, Rigbolt K T, Bunkenborg J, Cox J, Foster L J, Heck A J, Blagoev B, Andersen J S, Mann M (2010). MSQuant, an open source platform for mass spectrometry-based quantitative proteomics. J Proteome Res, 9(1): 393–403

DOI PMID

131
Moser K, White F M (2006). Phosphoproteomic analysis of rat liver by high capacity IMAC and LC-MS/MS. J Proteome Res, 5(1): 98–104

DOI PMID

132
Negroni L, Claverol S, Rosenbaum J, Chevet E, Bonneu M, Schmitter J M (2012). Comparison of IMAC and MOAC for phosphopeptide enrichment by column chromatography. J Chromatogr B Analyt Technol Biomed Life Sci, 891-892: 109–112

DOI PMID

133
Neilson K A, Ali N A, Muralidharan S, Mirzaei M, Mariani M, Assadourian G, Lee A, van Sluyter S C, Haynes P A (2011). Less label, more free: approaches in label-free quantitative mass spectrometry. Proteomics, 11(4): 535–553

DOI PMID

134
Nelson C A, Szczech J R, Xu Q, Lawrence M J, Jin S, Ge Y (2009). Mesoporous zirconium oxide nanomaterials effectively enrich phosphopeptides for mass spectrometry-based phosphoproteomics. Chem Commun (Camb), (43): 6607–6609

DOI PMID

135
Nita-Lazar A, Saito-Benz H, White F M (2008). Quantitative phosphoproteomics by mass spectrometry: past, present, and future. Proteomics, 8(21): 4433–4443

DOI PMID

136
Nuhse T, Yu K, Salomon A (2007). Isolation of phosphopeptides by immobilized metal ion affinity chromatography. Curr Protoc Mol Biol, Chapter 18:13–18

137
Nuhse T S, Stensballe A, Jensen O N, Peck S C (2003). Large-scale analysis of in vivo phosphorylated membrane proteins by immobilized metal ion affinity chromatography and mass spectrometry. Mol Cell Proteomics, 2(11): 1234–1243

DOI PMID

138
Olsen J V, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (2006). Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell, 127(3): 635–648

DOI PMID

139
Olsen J V, Macek B, Lange O, Makarov A, Horning S, Mann M (2007). Higher-energy C-trap dissociation for peptide modification analysis. Nat Methods, 4(9): 709–712

DOI PMID

140
Olsen J V, Ong S E, Mann M (2004). Trypsin cleaves exclusively C-terminal to arginine and lysine residues. Mol Cell Proteomics, 3(6): 608–614

DOI PMID

141
Ong S E, Blagoev B, Kratchmarova I, Kristensen D B, Steen H, Pandey A, Mann M (2002). Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol Cell Proteomics, 1(5): 376–386

DOI PMID

142
Ong S E, Foster L J, Mann M (2003a). Mass spectrometric-based approaches in quantitative proteomics. Methods, 29(2): 124–130

DOI PMID

143
Ong S E, Kratchmarova I, Mann M (2003b). Properties of 13C-substituted arginine in stable isotope labeling by amino acids in cell culture (SILAC). J Proteome Res, 2(2): 173–181

DOI PMID

144
Ong S E, Mann M (2005). Mass spectrometry-based proteomics turns quantitative. Nat Chem Biol, 1(5): 252–262

DOI PMID

145
Ong S E, Mann M (2006). A practical recipe for stable isotope labeling by amino acids in cell culture (SILAC). Nat Protoc, 1(6): 2650–2660

DOI PMID

146
Ong S E, Mann M (2007). Stable isotope labeling by amino acids in cell culture for quantitative proteomics. Methods Mol Biol, 359: 37–52

DOI PMID

147
Oyama M, Nagashima T, Suzuki T, Kozuka-Hata H, Yumoto N, Shiraishi Y, Ikeda K, Kuroki Y, Gotoh N, Ishida T, Inoue S, Kitano H, Okada-Hatakeyama M (2011). Integrated quantitative analysis of the phosphoproteome and transcriptome in tamoxifen-resistant breast cancer. J Biol Chem, 286(1): 818–829

DOI PMID

148
Palumbo A M, Smith S A, Kalcic C L, Dantus M, Stemmer P M, Reid G E (2011). Tandem mass spectrometry strategies for phosphoproteome analysis. Mass Spectrom Rev, 30(4): 600–625

DOI PMID

149
Pan C, Olsen J V, Daub H, Mann M (2009). Global effects of kinase inhibitors on signaling networks revealed by quantitative phosphoproteomics. Mol Cell Proteomics, 8(12): 2796–2808

DOI PMID

150
Peng J, Elias J E, Thoreen C C, Licklider L J, Gygi S P (2003). Evaluation of multidimensional chromatography coupled with tandem mass spectrometry (LC/LC-MS/MS) for large-scale protein analysis: the yeast proteome. J Proteome Res, 2(1): 43–50

DOI PMID

151
Perkins D N, Pappin D J, Creasy D M, Cottrell J S (1999). Probability-based protein identification by searching sequence databases using mass spectrometry data. Electrophoresis, 20(18): 3551–3567

DOI PMID

152
Pichler P, Köcher T, Holzmann J, Mazanek M, Taus T, Ammerer G, Mechtler K (2010). Peptide labeling with isobaric tags yields higher identification rates using iTRAQ 4-plex compared to TMT 6-plex and iTRAQ 8-plex on LTQ Orbitrap. Anal Chem, 82(15): 6549–6558

DOI PMID

153
Pimienta G, Chaerkady R, Pandey A (2009). SILAC for global phosphoproteomic analysis. Methods Mol Biol, 527: 107–116, x

DOI PMID

154
Pinkse M W, Uitto P M, Hilhorst M J, Ooms B, Heck A J (2004). Selective isolation at the femtomole level of phosphopeptides from proteolytic digests using 2D-NanoLC-ESI-MS/MS and titanium oxide precolumns. Anal Chem, 76(14): 3935–3943

DOI PMID

155
Posewitz M C, Tempst P (1999). Immobilized gallium(III) affinity chromatography of phosphopeptides. Anal Chem, 71(14): 2883–2892

DOI PMID

156
Pottiez G, Wiederin J, Fox H S, Ciborowski P (2012). Comparison of 4-plex to 8-plex iTRAQ quantitative measurements of proteins in human plasma samples. J Proteome Res, 11(7): 3774–3781

DOI PMID

157
Powell S N, Kachnic L A (2008). Therapeutic exploitation of tumor cell defects in homologous recombination. Anticancer Agents Med Chem, 8(4): 448–460

PMID

158
Reid G E, McLuckey S A (2002). ‘Top down’ protein characterization via tandem mass spectrometry. J Mass Spectrom, 37(7): 663–675

DOI PMID

159
Rohrig H, Colby T, Schmidt J, Harzen A, Facchinelli F, Bartels D (2008). Analysis of desiccation-induced candidate phosphoproteins from Craterostigma plantagineum isolated with a modified metal oxide affinity chromatography procedure. Proteomics, 8(17): 3548–3560

DOI PMID

160
Rosenqvist H, Ye J, Jensen O N (2011). Analytical strategies in mass spectrometry-based phosphoproteomics. Methods Mol Biol, 753: 183–213

DOI PMID

161
Ross P L, Huang Y N, Marchese J N, Williamson B, Parker K, Hattan S, Khainovski N, Pillai S, Dey S, Daniels S, Purkayastha S, Juhasz P, Martin S, Bartlet-Jones M, He F, Jacobson A, Pappin D J (2004). Multiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagents. Mol Cell Proteomics, 3(12): 1154–1169

DOI PMID

162
Ruan L, Li X H, Wan X X, Yi H, Li C, Li M Y, Zhang P F, Zeng G Q, Qu J Q, He Q Y, Li J H, Chen Y, Chen Z C, Xiao Z Q (2011). Analysis of EGFR signaling pathway in nasopharyngeal carcinoma cells by quantitative phosphoproteomics. Proteome Sci, 9(1): 35

DOI PMID

163
Rudrabhatla P, Grant P, Jaffe H, Strong M J, Pant H C (2010). Quantitative phosphoproteomic analysis of neuronal intermediate filament proteins (NF-M/H) in Alzheimer’s disease by iTRAQ. FASEB J, 24(11): 4396–4407

DOI PMID

164
Ruttenberg B E, Pisitkun T, Knepper M A, Hoffert J D (2008). PhosphoScore: an open-source phosphorylation site assignment tool for MSn data. J Proteome Res, 7(7): 3054–3059

DOI PMID

165
Savitski M M, Lemeer S, Boesche M, Lang M, Mathieson T, Bantscheff M, Kuster B (2011). Confident phosphorylation site localization using the Mascot Delta Score. Mol Cell Proteomics, 10(2):M110.03830

166
Schlosser A, Pipkorn R, Bossemeyer D, Lehmann W D (2001). Analysis of protein phosphorylation by a combination of elastase digestion and neutral loss tandem mass spectrometry. Anal Chem, 73(2): 170–176

DOI PMID

167
Schlosser A, Vanselow J T, Kramer A (2005). Mapping of phosphorylation sites by a multi-protease approach with specific phosphopeptide enrichment and NanoLC-MS/MS analysis. Anal Chem, 77(16): 5243–5250

DOI PMID

168
Scholten A, Mohammed S, Low T Y, Zanivan S, van Veen T A, Delanghe B, Heck A J (2011). In-depth quantitative cardiac proteomics combining electron transfer dissociation and the metalloendopeptidase Lys-N with the SILAC mouse. Mol Cell Proteomics, 10(10):O111.008474

169
Schroeder M J, Shabanowitz J, Schwartz J C, Hunt D F, Coon J J (2004). A neutral loss activation method for improved phosphopeptide sequence analysis by quadrupole ion trap mass spectrometry. Anal Chem, 76(13): 3590–3598

DOI PMID

170
Schwacke J H, Hill E G, Krug E L, Comte-Walters S, Schey K L (2009). iQuantitator: a tool for protein expression inference using iTRAQ. BMC Bioinformatics, 10(1): 342

DOI PMID

171
Seeley E H, Riggs L D, Regnier F E (2005). Reduction of non-specific binding in Ga(III) immobilized metal affinity chromatography for phosphopeptides by using endoproteinase Glu-C as the digestive enzyme. J Chromatogr B Analyt Technol Biomed Life Sci, 817(1): 81–88

DOI PMID

172
Semaan S M, Wang X, Stewart P A, Marshall A G, Sang Q X (2011). Differential phosphopeptide expression in a benign breast tissue, and triple-negative primary and metastatic breast cancer tissues from the same African-American woman by LC-LTQ/FT-ICR mass spectrometry. Biochem Biophys Res Commun, 412(1): 127–131

DOI PMID

173
Sethuraman M, McComb M E, Huang H, Huang S, Heibeck T, Costello C E, Cohen R A (2004). Isotope-coded affinity tag (ICAT) approach to redox proteomics: identification and quantitation of oxidant-sensitive cysteine thiols in complex protein mixtures. J Proteome Res, 3(6): 1228–1233

DOI PMID

174
Shilov I V, Seymour S L, Patel A A, Loboda A, Tang W H, Keating S P, Hunter C L, Nuwaysir L M, Schaeffer D A (2007). The Paragon Algorithm, a next generation search engine that uses sequence temperature values and feature probabilities to identify peptides from tandem mass spectra. Mol Cell Proteomics, 6(9): 1638–1655

DOI PMID

175
Simon E S, Young M, Chan A, Bao Z Q, Andrews P C (2008). Improved enrichment strategies for phosphorylated peptides on titanium dioxide using methyl esterification and pH gradient elution. Anal Biochem, 377(2): 234–242

DOI PMID

177
Siuti N, Kelleher N L (2007). Decoding protein modifications using top-down mass spectrometry. Nat Methods, 4(10): 817–821

DOI PMID

178
Steen H, Jebanathirajah J A, Springer M, Kirschner M W (2005). Stable isotope-free relative and absolute quantitation of protein phosphorylation stoichiometry by MS. Proc Natl Acad Sci USA, 102(11): 3948–3953

DOI PMID

179
Stensballe A, Jensen O N (2004). Phosphoric acid enhances the performance of Fe(III) affinity chromatography and matrix-assisted laser desorption/ionization tandem mass spectrometry for recovery, detection and sequencing of phosphopeptides. Rapid Commun Mass Spectrom, 18(15): 1721–1730

DOI PMID

180
Stupak J, Liu H, Wang Z, Brix B J, Fliegel L, Li L (2005). Nanoliter sample handling combined with microspot MALDI-MS for detection of gel-separated phosphoproteins. J Proteome Res, 4(2): 515–522

DOI PMID

181
Sugiyama N, Masuda T, Shinoda K, Nakamura A, Tomita M, Ishihama Y (2007). Phosphopeptide enrichment by aliphatic hydroxy acid-modified metal oxide chromatography for nano-LC-MS/MS in proteomics applications. Mol Cell Proteomics, 6(6): 1103–1109

DOI PMID

182
Sui S, Wang J, Lu Z, Cai Y, Zhang Y, Yu W, Qian X (2008). Phosphopeptide enrichment strategy based on strong cation exchange chromatography. Se Pu, 26(2): 195–199

DOI PMID

183
Swaney D L, McAlister G C, Wirtala M, Schwartz J C, Syka J E, Coon J J (2007). Supplemental activation method for high-efficiency electron-transfer dissociation of doubly protonated peptide precursors. Anal Chem, 79(2): 477–485

DOI PMID

184
Sweet S M, Creese A J, Cooper H J (2006). Strategy for the identification of sites of phosphorylation in proteins: neutral loss triggered electron capture dissociation. Anal Chem, 78(21): 7563–7569

DOI PMID

185
Syka J E, Coon J J, Schroeder M J, Shabanowitz J, Hunt D F (2004a). Peptide and protein sequence analysis by electron transfer dissociation mass spectrometry. Proc Natl Acad Sci USA, 101(26): 9528–9533

DOI PMID

186
Syka J E, Marto J A, Bai D L, Horning S, Senko M W, Schwartz J C, Ueberheide B, Garcia B, Busby S, Muratore T, Shabanowitz J, Hunt D F (2004b). 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, 3(3): 621–626

DOI PMID

188
Taouatas N, Mohammed S, Heck A J (2011). Exploring new proteome space: combining Lys-N proteolytic digestion and strong cation exchange (SCX) separation in peptide-centric MS-driven proteomics. Methods Mol Biol, 753: 157–167

DOI PMID

189
Tasaki S, Nagasaki M, Kozuka-Hata H, Semba K, Gotoh N, Hattori S, Inoue J, Yamamoto T, Miyano S, Sugano S, Oyama M (2010). Phosphoproteomics-based modeling defines the regulatory mechanism underlying aberrant EGFR signaling. PLoS ONE, 5(11): e13926

DOI PMID

190
Taus T, Köcher T, Pichler P, Paschke C, Schmidt A, Henrich C, Mechtler K (2011). Universal and confident phosphorylation site localization using phosphoRS. J Proteome Res, 10(12): 5354–5362

DOI PMID

191
Thingholm T E, Jensen O N, Larsen M R (2009). Analytical strategies for phosphoproteomics. Proteomics, 9(6): 1451–1468

DOI PMID

192
Thingholm T E, Jensen O N, Robinson P J, Larsen M R (2008). SIMAC (sequential elution from IMAC), a phosphoproteomics strategy for the rapid separation of monophosphorylated from multiply phosphorylated peptides. Mol Cell Proteomics, 7(4): 661–671

DOI PMID

193
Thingholm T E, Jørgensen T J, Jensen O N, Larsen M R (2006). Highly selective enrichment of phosphorylated peptides using titanium dioxide. Nat Protoc, 1(4): 1929–1935

DOI PMID

194
Thompson A, Schäfer J, Kuhn K, Kienle S, Schwarz J, Schmidt G, Neumann T, Johnstone R, Mohammed A K, Hamon C (2003). Tandem mass tags: a novel quantification strategy for comparative analysis of complex protein mixtures by MS/MS. Anal Chem, 75(8): 1895–1904

DOI PMID

195
Villa S, De Fazio G, Canosi U (1989). Cyanogen bromide cleavage at methionine residues of polypeptides containing disulfide bonds. Anal Biochem, 177(1): 161–164

DOI PMID

196
Villen J, Beausoleil S A, Gerber S A, Gygi S P (2007). Large-scale phosphorylation analysis of mouse liver. Proc Natl Acad Sci USA, 104(5): 1488–1493

DOI PMID

197
Villen J, Gygi S P (2008). The SCX/IMAC enrichment approach for global phosphorylation analysis by mass spectrometry. Nat Protoc, 3(10): 1630–1638

DOI PMID

198
Wang G, Wu W W, Zeng W, Chou C L, Shen R F (2006). Label-free protein quantification using LC-coupled ion trap or FT mass spectrometry: Reproducibility, linearity, and application with complex proteomes. J Proteome Res, 5(5): 1214–1223

DOI PMID

199
Wang S, Basson M D (2011). Akt directly regulates focal adhesion kinase through association and serine phosphorylation: implication for pressure-induced colon cancer metastasis. Am J Physiol Cell Physiol, 300(3): C657–C670

DOI PMID

200
Wang X, Stewart P A, Cao Q, Sang Q X, Chung L W, Emmett M R, Marshall A G (2011). Characterization of the phosphoproteome in androgen-repressed human prostate cancer cells by Fourier transform ion cyclotron resonance mass spectrometry. J Proteome Res, 10(9): 3920–3928

DOI PMID

201
Wang Y T, Tsai C F, Hong T C, Tsou C C, Lin P Y, Pan S H, Hong T M, Yang P C, Sung T Y, Hsu W L, Chen Y J (2010). An informatics-assisted label-free quantitation strategy that depicts phosphoproteomic profiles in lung cancer cell invasion. J Proteome Res, 9(11): 5582–5597

DOI PMID

202
Washburn M P, Wolters D, Yates J R 3rd (2001). Large-scale analysis of the yeast proteome by multidimensional protein identification technology. Nat Biotechnol, 19(3): 242–247

DOI PMID

203
Whitelegge J, Halgand F, Souda P, Zabrouskov V (2006). Top-down mass spectrometry of integral membrane proteins. Expert Rev Proteomics, 3(6): 585–596

DOI PMID

204
Wolschin F, Weckwerth W (2005). Combining metal oxide affinity chromatography (MOAC) and selective mass spectrometry for robust identification of in vivo protein phosphorylation sites. Plant Methods, 1(1): 9

DOI PMID

205
Wolschin F, Wienkoop S, Weckwerth W (2005). Enrichment of phosphorylated proteins and peptides from complex mixtures using metal oxide/hydroxide affinity chromatography (MOAC). Proteomics, 5(17): 4389–4397

DOI PMID

206
Wu J, Shakey Q, Liu W, Schuller A, Follettie M T (2007). Global profiling of phosphopeptides by titania affinity enrichment. J Proteome Res, 6(12): 4684–4689

DOI PMID

207
Wu J, Warren P, Shakey Q, Sousa E, Hill A, Ryan T E, He T (2010). Integrating titania enrichment, iTRAQ labeling, and Orbitrap CID-HCD for global identification and quantitative analysis of phosphopeptides. Proteomics, 10(11): 2224–2234

DOI PMID

208
Xiao G G, Recker R R, Deng H W (2008). Recent advances in proteomics and cancer biomarker discovery. Clin Med Oncol, 2: 63–72

PMID

209
Xie X, Feng S, Vuong H, Liu Y, Goodison S, Lubman D M (2010). A comparative phosphoproteomic analysis of a human tumor metastasis model using a label-free quantitative approach. Electrophoresis, 31(11): 1842–1852

DOI PMID

210
Xu Y M, Zhu F, Cho Y Y, Carper A, Peng C, Zheng D, Yao K, Lau A T, Zykova T A, Kim H G, Bode A M, Dong Z (2010). Extracellular signal-regulated kinase 8-mediated c-Jun phosphorylation increases tumorigenesis of human colon cancer. Cancer Res, 70(8): 3218–3227

DOI PMID

211
Yachie N, Saito R, Sugahara J, Tomita M, Ishihama Y (2009). In silico analysis of phosphoproteome data suggests a rich-get-richer process of phosphosite accumulation over evolution. Mol Cell Proteomics, 8(5): 1061–1071

DOI PMID

212
Yan W, Lee H, Deutsch E W, Lazaro C A, Tang W, Chen E, Fausto N, Katze M G, Aebersold R (2004). A dataset of human liver proteins identified by protein profiling via isotope-coded affinity tag (ICAT) and tandem mass spectrometry. Mol Cell Proteomics, 3(10): 1039–1041

DOI PMID

213
Yang F, Wu S, Stenoien D L, Zhao R, Monroe M E, Gritsenko M A, Purvine S O, Polpitiya A D, Tolić N, Zhang Q, Norbeck A D, Orton D J, Moore R J, Tang K, Anderson G A, Pasa-Tolić L, Camp D G 2nd, Smith R D (2009). Combined pulsed-Q dissociation and electron transfer dissociation for identification and quantification of iTRAQ-labeled phosphopeptides. Anal Chem, 81(10): 4137–4143

DOI PMID

214
Yang X J (2005). Multisite protein modification and intramolecular signaling. Oncogene, 24(10): 1653–1662

DOI PMID

215
Yates J R, Cociorva D, Liao L, Zabrouskov V (2006). Performance of a linear ion trap-Orbitrap hybrid for peptide analysis. Anal Chem, 78(2): 493–500

DOI PMID

216
Yates J R 3rd, Eng J K, McCormack A L, Schieltz D (1995). Method to correlate tandem mass spectra of modified peptides to amino acid sequences in the protein database. Anal Chem, 67(8): 1426–1436

DOI PMID

217
Yi E C, Li X J, Cooke K, Lee H, Raught B, Page A, Aneliunas V, Hieter P, Goodlett D R, Aebersold R (2005). Increased quantitative proteome coverage with (13)C/(12)C-based, acid-cleavable isotope-coded affinity tag reagent and modified data acquisition scheme. Proteomics, 5(2): 380–387

DOI PMID

218
Yu L R, Issaq H J, Veenstra T D (2007). Phosphoproteomics for the discovery of kinases as cancer biomarkers and drug targets. Proteomics Clin Appl, 1(9): 1042–1057

DOI PMID

219
Yu P T, Babicky M, Jaquish D, French R, Marayuma K, Mose E, Niessen S, Hoover H, Shields D, Cheresh D, Cravatt B F, Lowy A M (2012). The RON-receptor regulates pancreatic cancer cell migration through phosphorylation-dependent breakdown of the hemidesmosome. Int J Cancer, 131(8): 1744–1754

DOI PMID

220
Yu Y P, Luo J H (2011). Phosphorylation and interaction of myopodin by integrin-link kinase lead to suppression of cell growth and motility in prostate cancer cells. Oncogene, 30(49): 4855–4863

DOI PMID

221
Yu Z, Han G, Sun S, Jiang X, Chen R, Wang F, Wu R, Ye M, Zou H (2009). Preparation of monodisperse immobilized Ti(4+) affinity chromatography microspheres for specific enrichment of phosphopeptides. Anal Chim Acta, 636(1): 34–41

DOI PMID

222
Zanivan S, Krueger M, Mann M (2012). In vivo quantitative proteomics: the SILAC mouse. Methods Mol Biol, 757: 435–450

DOI PMID

223
Zarei M, Sprenger A, Gretzmeier C, Dengjel J (2012). Combinatorial use of electrostatic repulsion-hydrophilic interaction chromatography (ERLIC) and strong cation exchange (SCX) chromatography for in-depth phosphoproteome analysis. J Proteome Res, 11(8): 4269–4276

DOI PMID

224
Zgoła-Grzeskowiak A, Grzeskowiak T (2011). The use of a triple quadrupole linear ion trap mass spectrometer with electrospray ionisation for fragmentation studies of selected antifungal drugs. Rapid Commun Mass Spectrom, 25(20): 3049–3055

DOI PMID

225
Zhai B, Villén J, Beausoleil S A, Mintseris J, Gygi S P (2008). Phosphoproteome analysis of Drosophila melanogaster embryos. J Proteome Res, 7(4): 1675–1682

DOI PMID

226
Zhang G, Fang B, Liu R Z, Lin H, Kinose F, Bai Y, Oguz U, Remily-Wood E R, Li J, Altiok S, Eschrich S, Koomen J, Haura E B (2011a). Mass spectrometry mapping of epidermal growth factor receptor phosphorylation related to oncogenic mutations and tyrosine kinase inhibitor sensitivity. J Proteome Res, 10(1): 305–319

DOI PMID

227
Zhang P X, Wang Y, Liu Y, Jiang G Y, Li Q C, Wang E H (2011b). p120-catenin isoform 3 regulates subcellular localization of Kaiso and promotes invasion in lung cancer cells via a phosphorylation-dependent mechanism. Int J Oncol, 38(6): 1625–1635

PMID

228
Zhao S, Venkatasubbarao K, Lazor J W, Sperry J, Jin C, Cao L, Freeman J W (2008). Inhibition of STAT3 Tyr705 phosphorylation by Smad4 suppresses transforming growth factor beta-mediated invasion and metastasis in pancreatic cancer cells. Cancer Res, 68(11): 4221–4228

DOI PMID

229
Zhong J, Kim M S, Chaerkady R, Wu X, Huang T C, Getnet D, Mitchell C J, Palapetta S M, Sharma J, O'Meally R N, Cole R N, Yoda A, Moritz A, Loriaux M M, Rush J, Weinstock D M, Tyner J W, Pandey A (2012). TSLP signaling network revealed by SILAC-based phosphoproteomics. Mol Cell Proteomics, 11(6):M112.017764

230
Zhou H, Tian R, Ye M, Xu S, Feng S, Pan C, Jiang X, Li X, Zou H (2007). Highly specific enrichment of phosphopeptides by zirconium dioxide nanoparticles for phosphoproteome analysis. Electrophoresis, 28(13): 2201–2215

DOI PMID

231
Zhou H, Ye M, Dong J, Han G, Jiang X, Wu R, Zou H (2008). Specific phosphopeptide enrichment with immobilized titanium ion affinity chromatography adsorbent for phosphoproteome analysis. J Proteome Res, 7(9): 3957–3967

DOI PMID

232
Zhou W, Capello M, Fredolini C, Piemonti L, Liotta L A, Novelli F, Petricoin E F (2011). Proteomic analysis of pancreatic ductal adenocarcinoma cells reveals metabolic alterations. J Proteome Res, 10(4): 1944–1952

DOI PMID

233
Zhou W, Capello M, Fredolini C, Racanicchi L, Piemonti L, Liotta L A, Novelli F, Petricoin E F (2012a). Proteomic analysis reveals Warburg effect and anomalous metabolism of glutamine in pancreatic cancer cells. J Proteome Res, 11(2): 554–563

DOI PMID

234
Zhou W, Liotta L A, Petricoin E F (2012b). The spectra count label-free quantitation in cancer proteomics. Cancer Genomics Proteomics, 9(3): 135–142

PMID

235
Zubarev R A (2004). Electron-capture dissociation tandem mass spectrometry. Curr Opin Biotechnol, 15(1):12–16

Outlines

/