PTMScan direct: Identification and quantification of peptides from critical signaling proteins by immunoaffinity enrichment coupled with LC-MS/MS

Molecular and Cellular Proteomics

Volumn 11, Issue 5, 2012, Pages 187-201

  Stokes, Matthew P ^a   Farnsworth, Charles L ^a   Moritz, Albrecht ^a   Silva, Jeffrey C ^a   Jia, Xiaoying ^a   Lee, Kimberly A ^a   Guo, Ailan ^a   Polakiewicz, Roberto D ^a   Comb, Michael J ^a  

^a CELL SIGNALING TECHNOLOGY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PHOSPHOPEPTIDE; PROTEIN KINASE B; PROTEIN SERINE KINASE; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE KINASE INHIBITOR;

ANIMAL TISSUE; ANTIBODY AFFINITY; CANCER CELL CULTURE; CONFERENCE PAPER; CONTROLLED STUDY; ENZYME SPECIFICITY; HUMAN; HUMAN CELL; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN PROCESSING; PROTEOMICS;

ANIMALS; BRAIN; CELL LINE; CHROMATOGRAPHY, AFFINITY; CHROMATOGRAPHY, LIQUID; EMBRYO, MAMMALIAN; HUMANS; IMMUNOPRECIPITATION; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; LIVER; MICE; MICE, INBRED BALB C; PEPTIDE FRAGMENTS; PEPTIDE MAPPING; PHOSPHOPROTEINS; PHOSPHORYLATION; PROTEIN INTERACTION MAPS; PROTEIN PROCESSING, POST-TRANSLATIONAL; RECEPTOR PROTEIN-TYROSINE KINASES; SIGNAL TRANSDUCTION; TANDEM MASS SPECTROMETRY;

EID: 84861161220     PISSN: 15359476     EISSN: 15359484     Source Type: Journal    
DOI: 10.1074/mcp.M111.015883     Document Type: Conference Paper

References (90)

1. Dowell, J. E., and Minna, J. D. (2005) Chasing mutations in the epidermal growth factor in lung cancer. N. Engl. J. Med. 352, 830-832 (Pubitemid 40271180)
2. Gazdar, A. F. (2009) Activating and resistance mutations of EGFR in non-small-cell lung cancer: Role in clinical response to EGFR tyrosine kinase inhibitors. Oncogene 28, (Suppl. 1) S24-S31
3. Guo, A., Villén, J., Kornhauser, J., Lee, K. A., Stokes, M. P., Rikova, K., Possemato, A., Nardone, J., Innocenti, G., Wetzel, R., Wang, Y., Mac-Neill, J., Mitchell, J., Gygi, S. P., Rush, J., Polakiewicz, R. D., and Comb, M. J. (2008) Signaling networks assembled by oncogenic EGFR and c-Met. Proc. Natl. Acad. Sci. U.S.A. 105, 692-697 (Pubitemid 351171770)
4. Rikova, K., Guo, A., Zeng, Q., Possemato, A., Yu, J., Haack, H., Nardone, J., Lee, K., Reeves, C., Li, Y., Hu, Y., Tan, Z., Stokes, M., Sullivan, L., Mitchell, J., Wetzel, R., Macneill, J., Ren, J. M., Yuan, J., Bakalarski, C. E., Villen, J., Kornhauser, J. M., Smith, B., Li, D., Zhou, X., Gygi, S. P., Gu, T. L., Polakiewicz, R. D., Rush, J., and Comb, M. J. (2007) Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 131, 1190-1203 (Pubitemid 350235027)
5. Weinstein, I. B. (2002) Cancer. Addiction to oncogenes: The Achilles heal of cancer. Science 297, 63-64
6. Antonescu, C. R. (2011) The GIST paradigm: Lessons for other kinasedriven cancers. J. Pathol. 223, 251-261
7. Hodgkinson, V. C., Eagle, G. L., Drew, P. J., Lind, M. J., and Cawkwell, L. (2010) Biomarkers of chemotherapy resistance in breast cancer identified by proteomics: Current status. Cancer Lett. 294, 13-24
8. Sasaki, T., Koivunen, J., Ogino, A., Yanagita, M., Nikiforow, S., Zheng, W., Lathan, C., Marcoux, J. P., Du, J., Okuda, K., Capelletti, M., Shimamura, T., Ercan, D., Stumpfova, M., Xiao, Y., Weremowicz, S., Butaney, M., Heon, S., Wilner, K., Christensen, J. G., Eck, M. J., Wong, K. K., Lindeman, N., Gray, N. S., Rodig, S. J., and Jänne, P. A. (2011) A novel ALK secondary mutation and EGFR signaling cause resistance to ALK kinase inhibitors. Cancer Res. 71, 6051-6060
9. Shi, H., Kong, X., Ribas, A., and Lo, R. S. (2011) Combinatorial treatments that overcome PDGFRβ-driven resistance of melanoma cells to V600EBRAF inhibition. Cancer Res. 71, 5067-5074
10. Weisberg, E., Barrett, R., Liu, Q., Stone, R., Gray, N., and Griffin, J. D. (2009) FLT3 inhibition and mechanisms of drug resistance in mutant FLT3-positive AML. Drug Resist. Updat. 12, 81-89
11. Jones, S., Zhang, X., Parsons, D. W., Lin, J. C., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Kamiyama, H., Jimeno, A., Hong, S. M., Fu, B., Lin, M. T., Calhoun, E. S., Kamiyama, M., Walter, K., Nikolskaya, T., Nikolsky, Y., Hartigan, J., Smith, D. R., Hidalgo, M., Leach, S. D., Klein, A. P., Jaffee, E. M., Goggins, M., Maitra, A., Iacobuzio-Donahue, C., Eshleman, J. R., Kern, S. E., Hruban, R. H., Karchin, R., Papadopoulos, N., Parmigiani, G., Vogelstein, B., Velculescu, V. E., and Kinzler, K. W. (2008) Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 321, 1801-1806
12. Luo, J., Solimini, N. L., and Elledge, S. J. (2009) Principles of cancer therapy: Oncogene and non-oncogene addiction. Cell 136, 823-837
13. Vogelstein, B., and Kinzler, K. W. (2004) Cancer genes and the pathways they control. Nat. Med. 10, 789-799 (Pubitemid 39070849)
14. LaFramboise, T. (2009) Single nucleotide polymorphism arrays: A decade of biological, computational and technological advances. Nucleic Acids Res. 37, 4181-4193
15. Maciejewski, J. P., Tiu, R. V., and O'Keefe, C. (2009) Application of array-based whole genome scanning technologies as a cytogenetic tool in haematological malignancies. Br. J. Haematol. 146, 479-488
16. Greenman, C., Stephens, P., Smith, R., Dalgliesh, G. L., Hunter, C., Bignell, G., Davies, H., Teague, J., Butler, A., Stevens, C., Edkins, S., O'Meara, S., Vastrik, I., Schmidt, E. E., Avis, T., Barthorpe, S., Bhamra, G., Buck, G., Choudhury, B., Clements, J., Cole, J., Dicks, E., Forbes, S., Gray, K., Halliday, K., Harrison, R., Hills, K., Hinton, J., Jenkinson, A., Jones, D., Menzies, A., Mironenko, T., Perry, J., Raine, K., Richardson, D., Shepherd, R., Small, A., Tofts, C., Varian, J., Webb, T., West, S., Widaa, S., Yates, A., Cahill, D. P., Louis, D. N., Goldstraw, P., Nicholson, A. G., Brasseur, F., Looijenga, L., Weber, B. L., Chiew, Y. E., DeFazio, A., Greaves, M. F., Green, A. R., Campbell, P., Birney, E., Easton, D. F., Chenevix-Trench, G., Tan, M. H., Khoo, S. K., Teh, B. T., Yuen, S. T., Leung, S. Y., Wooster, R., Futreal, P. A., and Stratton, M. R. (2007) Patterns of somatic mutation in human cancer genomes. Nature 446, 153-158 (Pubitemid 46398669)
17. Kan, Z., Jaiswal, B. S., Stinson, J., Janakiraman, V., Bhatt, D., Stern, H. M., Yue, P., Haverty, P. M., Bourgon, R., Zheng, J., Moorhead, M., Chaudhuri, S., Tomsho, L. P., Peters, B. A., Pujara, K., Cordes, S., Davis, D. P., Carlton, V. E., Yuan, W., Li, L., Wang, W., Eigenbrot, C., Kaminker, J. S., Eberhard, D. A., Waring, P., Schuster, S. C., Modrusan, Z., Zhang, Z., Stokoe, D., de Sauvage, F. J., Faham, M., and Seshagiri, S. (2010) Diverse somatic mutation patterns and pathway alterations in human cancers. Nature 466, 869-873
18. Puente, X. S., Pinyol, M., Quesada, V., Conde, L., Ordóñez, G. R., Villamor, N., Escaramis, G., Jares, P., Beá, S., González-Díaz, M., Bassaganyas, L., Baumann, T., Juan, M., López-Guerra, M., Colomer, D., Tubío, J. M., López, C., Navarro, A., Tornador, C., Aymerich, M., Rozman, M., Hernández, J. M., Puente, D. A., Freije, J. M., Velasco, G., Gutiérrez-Fernández, A., Costa, D., Carrió, A., Guijarro, S., Enjuanes, A., Hernández, L., Yagüe, J., Nicolás, P., Romeo-Casabona, C. M., Himmelbauer, H., Castillo, E., Dohm, J. C., de Sanjosé, S., Piris, M. A., de Alava, E., San Miguel, J., Royo, R., Gelpí, J. L., Torrents, D., Orozco, M., Pisano, D. G., Valencia, A., Guigó, R., Bayés, M., Heath, S., Gut, M., Klatt, P., Marshall, J., Raine, K., Stebbings, L. A., Futreal, P. A., Stratton, M. R., Campbell, P. J., Gut, I., López-Guillermo, A., Estivill, X., Montserrat, E., López-Otín, C., and Campo, E. (2011) Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia. Nature 475, 101-105
19. Chin, K., DeVries, S., Fridlyand, J., Spellman, P. T., Roydasgupta, R., Kuo, W. L., Lapuk, A., Neve, R. M., Qian, Z., Ryder, T., Chen, F., Feiler, H., Tokuyasu, T., Kingsley, C., Dairkee, S., Meng, Z., Chew, K., Pinkel, D., Jain, A., Ljung, B. M., Esserman, L., Albertson, D. G., Waldman, F. M., and Gray, J. W. (2006) Genomic and transcriptional aberrations linked to breast cancer pathophysiologies. Cancer Cell 10, 529-541 (Pubitemid 44854748)
20. Cantin, G. T., Yi, W., Lu, B., Park, S. K., Xu, T., Lee, J. D., and Yates, J. R., 3rd (2008) Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. J. Proteome Res. 7, 1346-1351
21. Lee, K. A., Hammerle, L. P., Andrews, P. S., Stokes, M. P., Mustelin, T., Silva, J. C., Black, R. A., and Doedens, J. R. (2011) Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels. J. Biol. Chem. 286, 41530-41538
22. Olsen, J. V., Blagoev, B., Gnad, F., Macek, B., Kumar, C., Mortensen, P., and Mann, M. (2006) Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 127, 635-648 (Pubitemid 44647421)
23. Choudhary, C., Kumar, C., Gnad, F., Nielsen, M. L., Rehman, M., Walther, T. C., Olsen, J. V., and Mann, M. (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325, 834-840
24. Choudhary, C., and Mann, M. (2010) Decoding signalling networks by mass spectrometry-based proteomics. Nat. Rev. Mol. Cell Biol. 11, 427-439
25. Denis, N. J., Vasilescu, J., Lambert, J. P., Smith, J. C., and Figeys, D. (2007) Tryptic digestion of ubiquitin standards reveals an improved strategy for identifying ubiquitinated proteins by mass spectrometry. Proteomics 7, 868-874 (Pubitemid 46506734)
26. Xu, G., Paige, J. S., and Jaffrey, S. R. (2010) Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling. Nat. Biotechnol. 28, 868-873
27. Peng, J., Schwartz, D., Elias, J. E., Thoreen, C. C., Cheng, D., Marsischky, G., Roelofs, J., Finley, D., and Gygi, S. P. (2003) A proteomics approach to understanding protein ubiquitination. Nat. Biotechnol. 21, 921-926 (Pubitemid 36936199)
28. Villén, J., Beausoleil, S. A., Gerber, S. A., and Gygi, S. P. (2007) Large-scale phosphorylation analysis of mouse liver. Proc. Natl. Acad. Sci. U.S.A. 104, 1488-1493 (Pubitemid 46214617)
29. Feng, S., Ye, M., Zhou, H., Jiang, X., Zou, H., and Gong, B. (2007) Immobilized zirconium ion affinity chromatography for specific enrichment of phosphopeptides in phosphoproteome analysis. Mol. Cell. Proteomics 6, 1656-1665 (Pubitemid 47506174)
30. Eyrich, B., Sickmann, A., and Zahedi, R. P. (2011) Catch me if you can: Mass spectrometry-based phosphoproteomics and quantification strategies. Proteomics 11, 554-570
31. Monetti, M., Nagaraj, N., Sharma, K., and Mann, M. (2011) Large-scale phosphosite quantification in tissues by a spike-in SILAC method. Nat. Methods 8, 655-658
32. Rigbolt, K. T., Prokhorova, T. A., Akimov, V., Henningsen, J., Johansen, P. T., Kratchmarova, I., Kassem, M., Mann, M., Olsen, J. V., and Blagoev, B. (2011) System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. 4, rs3
33. Mann, M., Ong, S. E., Grønborg, M., Steen, H., Jensen, O. N., and Pandey, A. (2002) Analysis of protein phosphorylation using mass spectrometry: Deciphering the phosphoproteome. Trends Biotechnol. 20, 261-268 (Pubitemid 34451062)
34. Tan, F., Zhang, Y., Mi, W., Wang, J., Wei, J., Cai, Y., and Qian, X. (2008) Enrichment of phosphopeptides by Fe3+-immobilized magnetic nanoparticles for phosphoproteome analysis of the plasma membrane of mouse liver. J. Proteome Res. 7, 1078-1087
35. Zhou, H., Tian, R., Ye, M., Xu, S., Feng, S., Pan, C., Jiang, X., Li, X., and Zou, H. (2007) Highly specific enrichment of phosphopeptides by zirconium dioxide nanoparticles for phosphoproteome analysis. Electrophoresis 28, 2201-2215 (Pubitemid 47065147)
36. Larsen, M. R., Thingholm, T. E., Jensen, O. N., Roepstorff, P., and Jørgensen, T. J. (2005) Highly selective enrichment of phosphorylated peptides from peptide mixtures using titanium dioxide microcolumns. Mol. Cell. Proteomics 4, 873-886 (Pubitemid 41309146)
37. Cao, P., and Stults, J. T. (2000) Mapping the phosphorylation sites of proteins using on-line immobilized metal affinity chromatography/capillary electrophoresis/electrospray ionization multiple stage tandem mass spectrometry. Rapid Commun. Mass Spectrom. 14, 1600-1606
38. Stensballe, A., Andersen, S., and Jensen, O. N. (2001) Characterization of phosphoproteins from electrophoretic gels by nanoscale FeIII affinity chromatography with off-line mass spectrometry analysis. Proteomics 1, 207-222 (Pubitemid 33586717)
39. Rush, J., Moritz, A., Lee, K. A., Guo, A., Goss, V. L., Spek, E. J., Zhang, H., Zha, X. M., Polakiewicz, R. D., and Comb, M. J. (2005) Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat. Biotechnol. 23, 94-101 (Pubitemid 41724631)
40. Stokes, M. P., Rush, J., Macneill, J., Ren, J. M., Sprott, K., Nardone, J., Yang, V., Beausoleil, S. A., Gygi, S. P., Livingstone, M., Zhang, H., Polakiewicz, R. D., and Comb, M. J. (2007) Profiling of UV-induced ATM/ATR signaling pathways. Proc. Natl. Acad. Sci. U.S.A. 104, 19855-19860
41. Zhang, H., Zha, X., Tan, Y., Hornbeck, P. V., Mastrangelo, A. J., Alessi, D. R., Polakiewicz, R. D., and Comb, M. J. (2002) Phosphoprotein analysis using antibodies broadly reactive against phosphorylated motifs. J. Biol. Chem. 277, 39379-39387 (Pubitemid 35190911)
42. Bonnette, P. C., Robinson, B. S., Silva, J. C., Stokes, M. P., Brosius, A. D., Baumann, A., and Buckbinder, L. (2010) Phosphoproteomic characterization of PYK2 signaling pathways involved in osteogenesis. J. Proteomics 73, 1306-1320
43. Moritz, A., Li, Y., Guo, A., Villén, J., Wang, Y., MacNeill, J., Kornhauser, J., Sprott, K., Zhou, J., Possemato, A., Ren, J. M., Hornbeck, P., Cantley, L. C., Gygi, S. P., Rush, J., and Comb, M. J. (2010) Akt-RSK-S6 kinase signaling networks activated by oncogenic receptor tyrosine kinases. Sci. Signal. 3, ra64
44. Brave, S. R., Ratcliffe, K., Wilson, Z., James, N. H., Ashton, S., Wainwright, A., Kendrew, J., Dudley, P., Broadbent, N., Sproat, G., Taylor, S., Barnes, C., Silva, J. C., Farnsworth, C. L., Hennequin, L., Ogilvie, D. J., Jürgensmeier, J. M., Shibuya, M., Wedge, S. R., and Barry, S. T. (2011) Assessing the activity of cediranib, a VEGFR-2/3 tyrosine kinase inhibitor, against VEGFR-1 and members of the structurally related PDGFR family. Mol. Cancer Ther. 10, 861-873
45. Olsen, J. V., de Godoy, L. M., Li, G., Macek, B., Mortensen, P., Pesch, R., Makarov, A., Lange, O., Horning, S., and Mann, M. (2005) Parts per million mass accuracy on an Orbitrap mass spectrometer via lock mass injection into a C-trap. Mol. Cell. Proteomics 4, 2010-2021 (Pubitemid 41830195)
46. Lundgren, D. H., Martinez, H., Wright, M. E., and Han, D. K. (2009) "Protein identification using Sorcerer 2 and SEQUEST," Current Protocols in Bioinformatics, Chapter 13, Unit 13.13 Wiley Blackwell USA
47. von Mering, C., Huynen, M., Jaeggi, D., Schmidt, S., Bork, P., and Snel, B. (2003) STRING: A database of predicted functional associations between proteins. Nucleic Acids Res. 31, 258-261
48. Kadota, S., Fantus, I. G., Deragon, G., Guyda, H. J., Hersh, B., and Posner, B. I. (1987) Peroxide(s) of vanadium: A novel and potent insulin-mimetic agent which activates the insulin receptor kinase. Biochem. Biophys. Res. Commun. 147, 259-266 (Pubitemid 17151966)
49. Fantus, I. G., Kadota, S., Deragon, G., Foster, B., and Posner, B. I. (1989) Pervanadate [peroxide 49(s) of vanadate] mimics insulin action in rat adipocytes via activation of the insulin receptor tyrosine kinase. Biochemistry 28, 8864-8871 (Pubitemid 19278548)
50. Manning, G., Whyte, D. B., Martinez, R., Hunter, T., and Sudarsanam, S. (2002) The protein kinase complement of the human genome. Science 298, 1912-1934 (Pubitemid 35425239)
51. Ackermann, B. L., Hale, J. E., and Duffin, K. L. (2006) The role of mass spectrometry in biomarker discovery and measurement. Curr. Drug Metab. 7, 525-539
52. Calligaris, D., Villard, C., and Lafitte, D. (2011) Advances in top-down proteomics for disease biomarker discovery. J. Proteomics 74, 920-934
53. Sawyers, C. L. (2002) Rational therapeutic intervention in cancer: Kinases as drug targets. Curr. Opin. Genet. Dev. 12, 111-115
54. Veenstra, T. D. (2007) Global and targeted quantitative proteomics for biomarker discovery. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 847, 3-11
55. Wu, Z., Doondeea, J. B., Moghaddas Gholami, A., Janning, M. C., Lemeer, S., Kramer, K., Eccles, S. A., Gollin, S. M., Grenman, R., Walch, A., Feller, S. M., and Kuster, B. (2011) Quantitative chemical proteomics reveals new potential drug targets in head and neck cancer. Mol. Cell. Proteomics 12, 10.1074/mcp.M111.011635
56. Lynch, T. J., Bell, D. W., Sordella, R., Gurubhagavatula, S., Okimoto, R. A., Brannigan, B. W., Harris, P. L., Haserlat, S. M., Supko, J. G., Haluska, F. G., Louis, D. N., Christiani, D. C., Settleman, J., and Haber, D. A. (2004) Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 350, 2129-2139 (Pubitemid 38637993)
57. Smolen, G. A., Sordella, R., Muir, B., Mohapatra, G., Barmettler, A., Archibald, H., Kim, W. J., Okimoto, R. A., Bell, D. W., Sgroi, D. C., Christensen, J. G., Settleman, J., and Haber, D. A. (2006) Amplification of MET may identify a subset of cancers with extreme sensitivity to the selective tyrosine kinase inhibitor PHA-665752. Proc. Natl. Acad. Sci. U.S.A. 103, 2316-2321
58. Tracy, S., Mukohara, T., Hansen, M., Meyerson, M., Johnson, B. E., and Jänne, P. A. (2004) Gefitinib induces apoptosis in the EGFRL858R nonsmall-cell lung cancer cell line H3255. Cancer Res. 64, 7241-7244 (Pubitemid 39372059)
59. Paez, J. G., Jänne, P. A., Lee, J. C., Tracy, S., Greulich, H., Gabriel, S., Herman, P., Kaye, F. J., Lindeman, N., Boggon, T. J., Naoki, K., Sasaki, H., Fujii, Y., Eck, M. J., Sellers, W. R., Johnson, B. E., and Meyerson, M. (2004) EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science 304, 1497-1500 (Pubitemid 38720929)
60. Shannon, P., Markiel, A., Ozier, O., Baliga, N. S., Wang, J. T., Ramage, D., Amin, N., Schwikowski, B., and Ideker, T. (2003) Cytoscape: A software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498-2504 (Pubitemid 37428274)
61. Kaji, M., Yonemura, Y., Harada, S., Liu, X., Terada, I., and Yamamoto, H. (1996) Participation of c-Met in the progression of human gastric cancers: Anti-c-Met oligonucleotides inhibit proliferation or invasiveness of gastric cancer cells. Cancer Gene Ther. 3, 393-404
62. Alessi, D. R., Andjelkovic, M., Caudwell, B., Cron, P., Morrice, N., Cohen, P., and Hemmings, B. A. (1996) Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J. 15, 6541-6551 (Pubitemid 26413787)
63. Bellacosa, A., Chan, T. O., Ahmed, N. N., Datta, K., Malstrom, S., Stokoe, D., McCormick, F., Feng, J., and Tsichlis, P. (1998) Akt activation by growth factors is a multiple-step process: The role of the PH domain. Oncogene 17, 313-325 (Pubitemid 28383008)
64. Stephens, L., Anderson, K., Stokoe, D., Erdjument-Bromage, H., Painter, G. F., Holmes, A. B., Gaffney, P. R., Reese, C. B., McCormick, F., Tempst, P., Coadwell, J., and Hawkins, P. T. (1998) Protein kinase B kinases that mediate phosphatidylinositol 3,4,5-trisphosphate-dependent activation of protein kinase B. Science 279, 710-714 (Pubitemid 28144551)
65. Vander Haar, E., Lee, S. I., Bandhakavi, S., Griffin, T. J., and Kim, D. H. (2007) Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40. Nat. Cell Biol. 9, 316-323 (Pubitemid 46344611)
66. Kovacina, K. S., Park, G. Y., Bae, S. S., Guzzetta, A. W., Schaefer, E., Birnbaum, M. J., and Roth, R. A. (2003) Identification of a proline-rich Akt substrate as a 14-3-3 binding partner. J. Biol. Chem. 278, 10189-10194 (Pubitemid 36800278)
67. Franke, T. F., Kaplan, D. R., and Cantley, L. C. (1997) PI3K: Downstream AKTion blocks apoptosis. Cell 88, 435-437 (Pubitemid 27154408)
68. Burgering, B. M., and Coffer, P. J. (1995) Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction. Nature 376, 599-602
69. Franke, T. F., Yang, S. I., Chan, T. O., Datta, K., Kazlauskas, A., Morrison, D. K., Kaplan, D. R., and Tsichlis, P. N. (1995) The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase. Cell 81, 727-736
70. Unsicker, K., and Krieglstein, K. (2006) Cell signaling and growth factors in development: From molecules to organogenesis, Wiley-VCH, Weinheim, Germany
71. Stokoe, D., Stephens, L. R., Copeland, T., Gaffney, P. R., Reese, C. B., Painter, G. F., Holmes, A. B., McCormick, F., and Hawkins, P. T. (1997) Dual role of phosphatidylinositol-3,4,5-trisphosphate in the activation of protein kinase B. Science 277, 567-570 (Pubitemid 27369005)
72. Easton, R. M., Cho, H., Roovers, K., Shineman, D. W., Mizrahi, M., Forman, M. S., Lee, V. M., Szabolcs, M., de Jong, R., Oltersdorf, T., Ludwig, T., Efstratiadis, A., and Birnbaum, M. J. (2005) Role for Akt3/protein kinase Bγ in attainment of normal brain size. Mol. Cell. Biol. 25, 1869-1878 (Pubitemid 40280150)
73. Tschopp, O., Yang, Z. Z., Brodbeck, D., Dummler, B. A., Hemmings-Mieszczak, M., Watanabe, T., Michaelis, T., Frahm, J., and Hemmings, B. A. (2005) Essential role of protein kinase B&gamma (PKB&gamma/Akt3) in postnatal brain development but not in glucose homeostasis. Development 132, 2943-2954 (Pubitemid 41086730)
74. Masure, S., Haefner, B., Wesselink, J. J., Hoefnagel, E., Mortier, E., Verhasselt, P., Tuytelaars, A., Gordon, R., and Richardson, A. (1999) Molecular cloning, expression and characterization of the human serine/threonine kinase Akt-3. Eur. J. Biochem. 265, 353-360 (Pubitemid 29466045)
75. Coffer, P. J., Jin, J., and Woodgett, J. R. (1998) Protein kinase B (c-Akt): A multifunctional mediator of phosphatidylinositol 3-kinase activation. Biochem. J. 335, 1-13 (Pubitemid 28477043)
76. Altomare, D. A., Guo, K., Cheng, J. Q., Sonoda, G., Walsh, K., and Testa, J. R. (1995) Cloning, chromosomal localization and expression analysis of the mouse Akt2 oncogene. Oncogene 11, 1055-1060
77. Altomare, D. A., Lyons, G. E., Mitsuuchi, Y., Cheng, J. Q., and Testa, J. R. (1998) Akt2 mRNA is highly expressed in embryonic brown fat and the AKT2 kinase is activated by insulin. Oncogene 16, 2407-2411 (Pubitemid 28226889)
78. Keranen, L. M., Dutil, E. M., and Newton, A. C. (1995) Protein kinase C is regulated in vivo by three functionally distinct phosphorylations. Curr. Biol. 5, 1394-1403 (Pubitemid 3008935)
79. Freeley, M., Kelleher, D., and Long, A. (2011) Regulation of protein kinase C function by phosphorylation on conserved and non-conserved sites. Cell Signal. 23, 753-762
80. Wetsel, W. C., Khan, W. A., Merchenthaler, I., Rivera, H., Halpern, A. E., Phung, H. M., Negro-Vilar, A., and Hannun, Y. A. (1992) Tissue and cellular distribution of the extended family of protein kinase C isoenzymes. J. Cell Biol. 117, 121-133
81. Wolf-Yadlin, A., Hautaniemi, S., Lauffenburger, D. A., and White, F. M. (2007) Multiple reaction monitoring for robust quantitative proteomic analysis of cellular signaling networks. Proc. Natl. Acad. Sci. U.S.A. 104, 5860-5865 (Pubitemid 47175624)
82. Anderson, L., and Hunter, C. L. (2006) Quantitative mass spectrometric multiple reaction monitoring assays for major plasma proteins. Mol. Cell. Proteomics 5, 573-588
83. Silva, J. C., Gorenstein, M. V., Li, G. Z., Vissers, J. P., and Geromanos, S. J. (2006) Absolute quantification of proteins by LCMSE: A virtue of parallel MS acquisition. Mol. Cell. Proteomics 5, 144-156 (Pubitemid 43169347)
84. Schmidt, A., Beck, M., Malmström, J., Lam, H., Claassen, M., Campbell, D., and Aebersold, R. (2011) Absolute quantification of microbial proteomes at different states by directed mass spectrometry. Mol. Syst. Biol. 7, 510-526
85. Reiter, L., Rinner, O., Picotti, P., Hüttenhain, R., Beck, M., Brusniak, M. Y., Hengartner, M. O., and Aebersold, R. (2011) mProphet: Automated data processing and statistical validation for large-scale SRM experiments. Nat. Methods 8, 430-435
86. Thakur, S. S., Geiger, T., Chatterjee, B., Bandilla, P., Frohlich, F., Cox, J., and Mann, M. (2011) Deep and highly sensitive proteome coverage by LC-MS/MS without prefractionation. Mol. Cell. Proteomics 10.1074/ mcp.M110.003699, 1-9
87. Whiteaker, J. R., Zhao, L., Abbatiello, S. E., Burgess, M., Kuhn, E., Lin, C., Pope, M. E., Razavi, M., Anderson, N. L., Pearson, T. W., Carr, S. A., and Paulovich, A. G. (2011) Evaluation of large scale quantitative proteomic assay development using peptide affinity-based mass spectrometry. Mol. Cell. Proteomics 10.1074/mcp.M110.005645
88. Anderson, N. L., Anderson, N. G., Pearson, T. W., Borchers, C. H., Paulovich, A. G., Patterson, S. D., Gillette, M., Aebersold, R., and Carr, S. A. (2009) A human proteome detection and quantitation project. Mol. Cell. Proteomics 8, 883-886
89. Michalski, A., Damoc, E., Hauschild, J. P., Lange, O., Wieghaus, A., Makarov, A., Nagaraj, N., Cox, J., Mann, M., and Horning, S. (2011) Mass spectrometry-based proteomics using Q Exactive, a high-performance benchtop quadrupole Orbitrap mass spectrometer. Mol. Cell. Proteomics 10.1074/M111.011015
90. Geiger, T., Cox, J., and Mann, M. (2010) Proteomics on an Orbitrap benchtop mass spectrometer using all-ion fragmentation. Mol. Cell. Proteomics 9, 2252-2261