title: Decoding signalling networks by mass spectrometry-based proteomics.
abstract: Signalling networks regulate essentially all of the biology of cells and organisms in normal and disease states. Signalling is often studied using antibody-based techniques such as western blots. Large-scale 'precision proteomics' based on mass spectrometry now enables the system-wide characterization of signalling events at the levels of post-translational modifications, protein-protein interactions and changes in protein expression. This technology delivers accurate and unbiased information about the quantitative changes of thousands of proteins and their modifications in response to any perturbation. Current studies focus on phosphorylation, but acetylation, methylation, glycosylation and ubiquitylation are also becoming amenable to investigation. Large-scale proteomics-based signalling research will fundamentally change our understanding of signalling networks.
authors.affiliation: The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. chuna.choudhary@cpr.ku.dk
authors.forename: Chunaram
authors.initials: C
authors.lastname: Choudhary
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
mesh_terms: D000818:Animals; D006801:Humans; D013058:Mass Spectrometry; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D015398:Signal Transduction
chemical_list: D020543:Proteome
references.citation: Cell Stem Cell. 2009 Aug 7;5(2):214-26
references.pmid: 19664995
references.citation: Science. 2005 Jun 3;308(5727):1472-7
references.pmid: 15933201
references.citation: Nat Biotechnol. 2006 Oct;24(10):1285-92
references.pmid: 16964243
references.citation: Science. 2009 Dec 11;326(5959):1502-9
references.pmid: 20007894
references.citation: Science. 2006 Mar 3;311(5765):1293-7
references.pmid: 16513984
references.citation: FEBS Lett. 2009 Jun 5;583(11):1703-12
references.pmid: 19306877
references.citation: Genes Dev. 2009 Aug 15;23(16):1929-43
references.pmid: 19684113
references.citation: Cell Host Microbe. 2009 Apr 23;5(4):397-403
references.pmid: 19380118
references.citation: Nat Methods. 2004 Nov;1(2):119-26
references.pmid: 15782174
references.citation: Cell. 2008 Jul 25;134(2):353-64
references.pmid: 18662549
references.citation: J Proteome Res. 2008 Sep;7(9):3900-10
references.pmid: 18698806
references.citation: Nature. 2003 Oct 16;425(6959):686-91
references.pmid: 14562095
references.citation: Genome Biol. 2007;8(11):R250
references.pmid: 18039369
references.citation: Nat Methods. 2007 Oct;4(10):798-806
references.pmid: 17901869
references.citation: Proteomics. 2008 Nov;8(21):4534-46
references.pmid: 18846507
references.citation: Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19855-60
references.pmid: 18077418
references.citation: Anal Chem. 2000 Feb 1;72(3):563-73
references.pmid: 10695143
references.citation: Nat Biotechnol. 2007 May;25(5):576-83
references.pmid: 17450130
references.citation: Sci Signal. 2009 May 26;2(72):ra24
references.pmid: 19471022
references.citation: Mol Syst Biol. 2005;1:2005.0008
references.pmid: 16729043
references.citation: Sci Signal. 2010 Jan 12;3(104):ra3
references.pmid: 20068231
references.citation: Nat Methods. 2009 Oct;6(10):741-4
references.pmid: 19749761
references.citation: Methods Mol Biol. 2010;604:55-71
references.pmid: 20013364
references.citation: Nat Rev Mol Cell Biol. 2004 Sep;5(9):699-711
references.pmid: 15340378
references.citation: Science. 2007 May 25;316(5828):1160-6
references.pmid: 17525332
references.citation: Science. 2009 Sep 25;325(5948):1682-6
references.pmid: 19779198
references.citation: Anal Chem. 1992 Jun 15;64(12):467R-502R
references.pmid: 1626707
references.citation: Mol Biosyst. 2009 Oct;5(10):1112-21
references.pmid: 19756300
references.citation: Cell. 2007 Dec 14;131(6):1190-203
references.pmid: 18083107
references.citation: Methods Mol Biol. 2010;604:273-83
references.pmid: 20013377
references.citation: Anal Chem. 2006 Apr 1;78(7):2113-20
references.pmid: 16579588
references.citation: Proteomics. 2009 Oct;9(20):4632-41
references.pmid: 19743430
references.citation: Nat Methods. 2006 Jul;3(7):533-9
references.pmid: 16791211
references.citation: Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18132-8
references.pmid: 18818311
references.citation: Cell. 2009 Aug 21;138(4):795-806
references.pmid: 19664813
references.citation: Nat Cell Biol. 2009 Dec;11(12):1458-64
references.pmid: 19935650
references.citation: Mol Cell. 2008 Aug 8;31(3):438-48
references.pmid: 18691976
references.citation: Nat Methods. 2010 May;7(5):383-5
references.pmid: 20364148
references.citation: Sci Signal. 2009 Jul 28;2(81):ra39
references.pmid: 19638616
references.citation: Nature. 2008 Oct 30;455(7217):1251-4
references.pmid: 18820680
references.citation: Mol Cell Proteomics. 2008 Sep;7(9):1763-77
references.pmid: 18515860
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10364-9
references.pmid: 17563356
references.citation: Immunity. 2010 Feb 26;32(2):279-89
references.pmid: 20171123
references.citation: Anal Chem. 2004 Jul 1;76(13):3590-8
references.pmid: 15228329
references.citation: Nature. 2003 Oct 16;425(6959):737-41
references.pmid: 14562106
references.citation: Nat Protoc. 2009;4(4):484-94
references.pmid: 19300442
references.citation: Curr Opin Chem Biol. 2009 Dec;13(5-6):510-7
references.pmid: 19775930
references.citation: Nat Methods. 2007 Sep;4(9):709-12
references.pmid: 17721543
references.citation: Nat Rev Mol Cell Biol. 2006 Dec;7(12):952-8
references.pmid: 17139335
references.citation: Proteomics. 2008 Nov;8(21):4433-43
references.pmid: 18846511
references.citation: Nature. 2001 May 17;411(6835):355-65
references.pmid: 11357143
references.citation: Mol Cell Proteomics. 2009 Jan;8(1):157-71
references.pmid: 18782753
references.citation: Nat Genet. 2000 May;25(1):25-9
references.pmid: 10802651
references.citation: Mol Cell Proteomics. 2008 Jan;7(1):132-44
references.pmid: 17938407
references.citation: Mol Cell Proteomics. 2009 Aug;8(8):1908-20
references.pmid: 19429919
references.citation: Nat Rev Mol Cell Biol. 2006 Jun;7(6):391-403
references.pmid: 16723975
references.citation: J Proteome Res. 2009 Oct;8(10):4553-63
references.pmid: 19691289
references.citation: Nat Biotechnol. 2008 Dec;26(12):1367-72
references.pmid: 19029910
references.citation: Nat Biotechnol. 2003 Mar;21(3):315-8
references.pmid: 12577067
references.citation: Science. 2009 Aug 14;325(5942):834-40
references.pmid: 19608861
references.citation: Mol Biosyst. 2009 Nov;5(11):1337-46
references.pmid: 19823750
references.citation: Proc Natl Acad Sci U S A. 2008 Apr 22;105(16):6069-74
references.pmid: 18420821
references.citation: Mol Cell Proteomics. 2009 Dec;8(12):2759-69
references.pmid: 19828875
references.citation: Annu Rev Pharmacol Toxicol. 2009;49:199-221
references.pmid: 18834307
references.citation: Mol Cell Proteomics. 2010 May;9(5):780-90
references.pmid: 20019052
references.citation: Nat Biotechnol. 2001 Mar;19(3):242-7
references.pmid: 11231557
references.citation: Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):5860-5
references.pmid: 17389395
references.citation: Science. 2006 Apr 14;312(5771):212-7
references.pmid: 16614208
references.citation: Mol Cell Proteomics. 2009 Dec;8(12):2796-808
references.pmid: 19651622
references.citation: Mol Cell Proteomics. 2005 Mar;4(3):310-27
references.pmid: 15665377
references.citation: Nat Biotechnol. 2007 Jan;25(1):125-31
references.pmid: 17195840
references.citation: Nat Biotechnol. 2003 Aug;21(8):921-6
references.pmid: 12872131
references.citation: Proc Natl Acad Sci U S A. 2009 Jan 27;106(4):995-1000
references.pmid: 19144917
references.citation: Cell Stem Cell. 2009 Aug 7;5(2):204-13
references.pmid: 19664994
references.citation: J Proteome Res. 2004 May-Jun;3(3):621-6
references.pmid: 15253445
references.citation: Mol Cell Proteomics. 2007 Aug;6(8):1416-27
references.pmid: 17510050
references.citation: Nat Biotechnol. 2008 Jan;26(1):127-32
references.pmid: 18183025
references.citation: Nat Rev Mol Cell Biol. 2007 Aug;8(8):645-54
references.pmid: 17593931
references.citation: Mol Cell Proteomics. 2005 Dec;4(12):2010-21
references.pmid: 16249172
references.citation: Mol Cell Proteomics. 2009 May;8(5):959-70
references.pmid: 19151416
references.citation: Nat Protoc. 2009;4(6):870-7
references.pmid: 19444244
references.citation: Nat Rev Mol Cell Biol. 2006 Jul;7(7):473-83
references.pmid: 16829979
references.citation: Mol Cell Proteomics. 2004 Dec;3(12):1154-69
references.pmid: 15385600
references.citation: Science. 2007 Nov 30;318(5855):1402-7
references.pmid: 18048679
references.citation: Anal Chem. 2003 Dec 15;75(24):6843-52
references.pmid: 14670044
references.citation: Curr Opin Biotechnol. 2008 Aug;19(4):331-7
references.pmid: 18590817
references.citation: Mol Cell. 2006 Aug;23(4):607-18
references.pmid: 16916647
references.citation: Immunity. 2009 Jan 16;30(1):143-54
references.pmid: 19144319
references.citation: Nat Biotechnol. 1999 Jul;17(7):676-82
references.pmid: 10404161
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2451-6
references.pmid: 18268350
references.citation: Nat Biotechnol. 2007 Sep;25(9):1035-44
references.pmid: 17721511
references.citation: Mol Cell Proteomics. 2002 May;1(5):376-86
references.pmid: 12118079
references.citation: Cell. 2006 Nov 3;127(3):635-48
references.pmid: 17081983
references.citation: Mol Syst Biol. 2009;5:237
references.pmid: 19156129
references.citation: Mol Cell. 2009 Apr 10;34(1):115-31
references.pmid: 19362540
references.citation: Nat Protoc. 2006;1(6):2856-60
references.pmid: 17406544
references.citation: Proc Natl Acad Sci U S A. 2009 Nov 10;106(45):18902-7
references.pmid: 19846766
references.citation: Sci Signal. 2009 Aug 18;2(84):ra46
references.pmid: 19690332
references.citation: Mol Cell Proteomics. 2007 Mar;6(3):377-81
references.pmid: 17164402
references.citation: Diabetes. 2006 Aug;55(8):2171-9
references.pmid: 16873679
references.citation: Nat Chem Biol. 2005 Oct;1(5):252-62
references.pmid: 16408053
references.citation: PLoS Comput Biol. 2007 Jan 5;3(1):e4
references.pmid: 17206861
references.citation: Nat Methods. 2009 May;6(5):359-62
references.pmid: 19377485
references.citation: Cell. 2007 Jun 29;129(7):1415-26
references.pmid: 17570479
references.citation: Mol Cell. 2009 Oct 23;36(2):326-39
references.pmid: 19854140
references.citation: Science. 2010 Feb 19;327(5968):1004-7
references.pmid: 20167787
references.citation: J Proteome Res. 2009 Nov;8(11):5347-55
references.pmid: 19754192
references.citation: Proc Natl Acad Sci U S A. 2008 Jan 15;105(2):692-7
references.pmid: 18180459
references.citation: Nucleic Acids Res. 2004 Jan 1;32(Database issue):D277-80
references.pmid: 14681412
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2009 May 1;877(13):1229-39
references.pmid: 19041286
references.citation: Nat Rev Mol Cell Biol. 2009 Sep;10(9):609-22
references.pmid: 19696798
references.citation: Mol Cell. 2007 Dec 14;28(5):730-8
references.pmid: 18082598
references.citation: Cell. 1996 Jun 14;85(6):817-27
references.pmid: 8681377
references.citation: Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7
references.pmid: 18669648
references.citation: Nature. 2009 Aug 6;460(7256):762-5
references.pmid: 19606093
references.citation: J Proteome Res. 2008 Dec;7(12):5314-26
references.pmid: 19367708
references.citation: Sci Signal. 2008 Sep 02;1(35):ra2
references.pmid: 18765831
references.citation: Sci Signal. 2010 Jan 12;3(104):ra2
references.pmid: 20068230
references.citation: Nat Biotechnol. 2004 Sep;22(9):1139-45
references.pmid: 15314609
references.citation: J Proteome Res. 2008 Mar;7(3):1118-30
references.pmid: 18271523
references.citation: Mol Cell Proteomics. 2008 Apr;7(4):672-83
references.pmid: 18045802
references.citation: Nat Methods. 2008 Jun;5(6):459-60
references.pmid: 18511913
references.citation: Mol Cell Proteomics. 2009 Mar;8(3):519-34
references.pmid: 19001411
references.citation: J Proteome Res. 2008 Jan;7(1):51-61
references.pmid: 18173218