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Phosphoproteomics Profiling to Identify Altered Signaling Pathways and Kinase-Targeted Cancer Therapies

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Mass Spectrometry Data Analysis in Proteomics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2051))

Abstract

Phosphorylation is one of the most extensively studied posttranslational modifications (PTM), which regulates cellular functions like cell growth, differentiation, apoptosis, and cell signaling. Kinase families cover a wide number of oncoproteins and are strongly associated with cancer. Identification of driver kinases is an intense area of cancer research. Thus, kinases serve as the potential target to improve the efficacy of targeted therapies. Mass spectrometry-based phosphoproteomic approach has paved the way to the identification of a large number of altered phosphorylation events in proteins and signaling cascades that may lead to oncogenic processes in a cell. Alterations in signaling pathways result in the activation of oncogenic processes predominantly regulated by kinases and phosphatases. Therefore, drugs such as kinase inhibitors, which target dysregulated pathways, represent a promising area for cancer therapy.

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References

  1. Duan G, Walther D (2015) The roles of post-translational modifications in the context of protein interaction networks. PLoS Comput Biol 11:e1004049

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Beltrao P, Bork P, Krogan NJ, Van Noort V (2013) Evolution and functional cross-talk of protein post-translational modifications. Mol Syst Biol 9:714

    Article  PubMed  PubMed Central  Google Scholar 

  3. Gavin AC, Bosche M, Krause R, Grandi P, Marzioch M, Bauer A et al (2002) Functional organization of the yeast proteome by systematic analysis of protein complexes. Nature 415:141–147

    Article  CAS  PubMed  Google Scholar 

  4. Kumar GK, Prabhakar NR (2008) Post-translational modification of proteins during intermittent hypoxia. Respir Physiol Neurobiol 164:272–276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Glavey SV, Huynh D, Reagan MR, Manier S, Moschetta M, Kawano Y et al (2015) The cancer glycome: carbohydrates as mediators of metastasis. Blood Rev 29:269–279

    Article  CAS  PubMed  Google Scholar 

  6. Gallo LH, Ko J, Donoghue DJ (2017) The importance of regulatory ubiquitination in cancer and metastasis. Cell Cycle 16:634–648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Singh V, Ram M, Kumar R, Prasad R, Roy BK, Singh KK (2017) Phosphorylation: implications in cancer. Protein J 36:1–6

    Article  CAS  PubMed  Google Scholar 

  8. Ardito F, Giuliani M, Perrone D, Troiano G, Lo Muzio L (2017) The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy (Review). Int J Mol Med 40:271–280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Nghiem HO, Bettendorff L, Changeux JP (2000) Specific phosphorylation of Torpedo 43K rapsyn by endogenous kinase(s) with thiamine triphosphate as the phosphate donor. FASEB J 14:543–554

    Article  CAS  PubMed  Google Scholar 

  10. Lemeer S, Heck AJ (2009) The phosphoproteomics data explosion. Curr Opin Chem Biol 13:414–420

    Article  CAS  PubMed  Google Scholar 

  11. Ubersax JA, Ferrell JE Jr (2007) Mechanisms of specificity in protein phosphorylation. Nat Rev Mol Cell Biol 8:530–541

    Article  CAS  PubMed  Google Scholar 

  12. Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70

    Article  CAS  PubMed  Google Scholar 

  13. Aebersold R, Mann M (2016) Mass-spectrometric exploration of proteome structure and function. Nature 537:347–355

    Article  CAS  PubMed  Google Scholar 

  14. Von Stechow L, Francavilla C, Olsen JV (2015) Recent findings and technological advances in phosphoproteomics for cells and tissues. Expert Rev Proteomics 12:469–487

    Article  CAS  Google Scholar 

  15. Harsha HC, Pandey A (2010) Phosphoproteomics in cancer. Mol Oncol 4:482–495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Lim YP (2005) Mining the tumor phosphoproteome for cancer markers. Clin Cancer Res 11:3163–3169

    Article  CAS  PubMed  Google Scholar 

  17. Corless CL, Fletcher JA, Heinrich MC (2004) Biology of gastrointestinal stromal tumors. J Clin Oncol 22:3813–3825

    Article  CAS  PubMed  Google Scholar 

  18. Javidi-Sharifi N, Traer E, Martinez J, Gupta A, Taguchi T, Dunlap J et al (2015) Crosstalk between KIT and FGFR3 promotes gastrointestinal stromal tumor cell growth and drug resistance. Cancer Res 75:880–891

    Article  CAS  PubMed  Google Scholar 

  19. Rikova K, Guo A, Zeng Q, Possemato A, Yu J, Haack H et al (2007) Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 131:1190–1203

    Article  CAS  PubMed  Google Scholar 

  20. Sharma SV, Bell DW, Settleman J, Haber DA (2007) Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 7:169–181

    Article  CAS  PubMed  Google Scholar 

  21. Zhu N, Xiao H, Wang LM, Fu S, Zhao C, Huang H (2015) Mutations in tyrosine kinase and tyrosine phosphatase and their relevance to the target therapy in hematologic malignancies. Future Oncol 11:659–673

    Article  CAS  PubMed  Google Scholar 

  22. Kraus J, Kraus M, Liu N, Besse L, Bader J, Geurink PP et al (2015) The novel beta2-selective proteasome inhibitor LU-102 decreases phosphorylation of I kappa B and induces highly synergistic cytotoxicity in combination with ibrutinib in multiple myeloma cells. Cancer Chemother Pharmacol 76:383–396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Jagarlamudi KK, Hansson LO, Eriksson S (2015) Breast and prostate cancer patients differ significantly in their serum Thymidine kinase 1 (TK1) specific activities compared with those hematological malignancies and blood donors: implications of using serum TK1 as a biomarker. BMC Cancer 15:66

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Hou S, Isaji T, Hang Q, Im S, Fukuda T, Gu J (2016) Distinct effects of beta1 integrin on cell proliferation and cellular signaling in MDA-MB-231 breast cancer cells. Sci Rep 6:18430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Paladino D, Yue P, Furuya H, Acoba J, Rosser CJ, Turkson J (2016) A novel nuclear Src and p300 signaling axis controls migratory and invasive behavior in pancreatic cancer. Oncotarget 7:7253–7267

    Article  PubMed  Google Scholar 

  26. Li Z, Lin P, Gao C, Peng C, Liu S, Gao H et al (2016) Integrin beta6 acts as an unfavorable prognostic indicator and promotes cellular malignant behaviors via ERK-ETS1 pathway in pancreatic ductal adenocarcinoma (PDAC). Tumour Biol 37:5117–5131

    Article  CAS  PubMed  Google Scholar 

  27. Mehraein-Ghomi F, Church DR, Schreiber CL, Weichmann AM, Basu HS, Wilding G (2015) Inhibitor of p52 NF-kappaB subunit and androgen receptor (AR) interaction reduces growth of human prostate cancer cells by abrogating nuclear translocation of p52 and phosphorylated AR(ser81). Genes Cancer 6:428–444

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Da Cunha Santos G, Shepherd FA, Tsao MS (2011) EGFR mutations and lung cancer. Annu Rev Pathol 6:49–69

    Article  PubMed  CAS  Google Scholar 

  29. Ludwig JA, Weinstein JN (2005) Biomarkers in cancer staging, prognosis and treatment selection. Nat Rev Cancer 5:845–856

    Article  CAS  PubMed  Google Scholar 

  30. Dancey JE (2006) Therapeutic targets: MTOR and related pathways. Cancer Biol Ther 5:1065–1073

    Article  CAS  PubMed  Google Scholar 

  31. Ahmadian MR (2002) Prospects for anti-ras drugs. Br J Haematol 116:511–518

    Article  CAS  PubMed  Google Scholar 

  32. Arora A, Scholar EM (2005) Role of tyrosine kinase inhibitors in cancer therapy. J Pharmacol Exp Ther 315:971–979

    Article  CAS  PubMed  Google Scholar 

  33. Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S et al (1996) Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med 2:561–566

    Article  CAS  PubMed  Google Scholar 

  34. Savage DG, Antman KH (2002) Imatinib mesylate--a new oral targeted therapy. N Engl J Med 346:683–693

    Article  CAS  PubMed  Google Scholar 

  35. Druker BJ, Sawyers CL, Kantarjian H, Resta DJ, Reese SF, Ford JM et al (2001) Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 344:1038–1042

    Article  CAS  PubMed  Google Scholar 

  36. Kantarjian H, Sawyers C, Hochhaus A, Guilhot F, Schiffer C, Gambacorti-Passerini C et al (2002) Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med 346:645–652

    Article  CAS  PubMed  Google Scholar 

  37. Antonicelli A, Cafarotti S, Indini A, Galli A, Russo A, Cesario A et al (2013) EGFR-targeted therapy for non-small cell lung cancer: focus on EGFR oncogenic mutation. Int J Med Sci 10:320–330

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S et al (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304:1497–1500

    Article  CAS  PubMed  Google Scholar 

  39. Yamamoto H, Toyooka S, Mitsudomi T (2009) Impact of EGFR mutation analysis in non-small cell lung cancer. Lung Cancer 63:315–321

    Article  PubMed  Google Scholar 

  40. Cancer Genome Atlas Research Network (2012) Comprehensive genomic characterization of squamous cell lung cancers. Nature 489:519–525

    Article  CAS  Google Scholar 

  41. Suda K, Onozato R, Yatabe Y, Mitsudomi T (2009) EGFR T790M mutation: a double role in lung cancer cell survival? J Thorac Oncol 4:1–4

    Article  PubMed  Google Scholar 

  42. Pao W, Miller VA, Politi KA, Riely GJ, Somwar R, Zakowski MF et al (2005) Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2:e73

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Gajria D, Chandarlapaty S (2011) HER2-amplified breast cancer: mechanisms of trastuzumab resistance and novel targeted therapies. Expert Rev Anticancer Ther 11:263–275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Chien AJ, Rugo HS (2017) Tyrosine kinase inhibitors for human epidermal growth factor receptor 2-positive metastatic breast cancer: is personalizing therapy within reach? J Clin Oncol 35:3089–3091

    Article  CAS  PubMed  Google Scholar 

  45. Wong KK, Fracasso PM, Bukowski RM, Lynch TJ, Munster PN, Shapiro GI et al (2009) A phase I study with neratinib (HKI-272), an irreversible pan ErbB receptor tyrosine kinase inhibitor, in patients with solid tumors. Clin Cancer Res 15:2552–2558

    Article  CAS  PubMed  Google Scholar 

  46. Mihaljevic A, Buchler P, Harder J, Hofheinz R, Gregor M, Kanzler S et al (2009) A prospective, non-randomized phase II trial of Trastuzumab and Capecitabine in patients with HER2 expressing metastasized pancreatic cancer. BMC Surg 9:1

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Walshe JM, Denduluri N, Berman AW, Rosing DR, Swain SM (2006) A phase II trial with trastuzumab and pertuzumab in patients with HER2-overexpressed locally advanced and metastatic breast cancer. Clin Breast Cancer 6:535–539

    Article  CAS  PubMed  Google Scholar 

  48. Harrington KJ, El-Hariry IA, Holford CS, Lusinchi A, Nutting CM, Rosine D et al (2009) Phase I study of lapatinib in combination with chemoradiation in patients with locally advanced squamous cell carcinoma of the head and neck. J Clin Oncol 27:1100–1107

    Article  CAS  PubMed  Google Scholar 

  49. Janne PA, Von Pawel J, Cohen RB, Crino L, Butts CA, Olson SS et al (2007) Multicenter, randomized, phase II trial of CI-1033, an irreversible pan-ERBB inhibitor, for previously treated advanced non small-cell lung cancer. J Clin Oncol 25:3936–3944

    Article  CAS  PubMed  Google Scholar 

  50. Petrelli A, Giordano S (2008) From single- to multi-target drugs in cancer therapy: when aspecificity becomes an advantage. Curr Med Chem. 15(5):422–432

    Article  CAS  PubMed  Google Scholar 

  51. Furman RR, Sharman JP, Coutre SE, Cheson BD, Pagel JM, Hillmen P, Barrientos JC, Zelenetz AD, Kipps TJ, Flinn I, Ghia P, Eradat H, Ervin T, Lamanna N, Coiffier B, Pettitt AR, Ma S, Stilgenbauer S, Cramer P, Aiello M, Johnson DM, Miller LL, Li D, Jahn TM, Dansey RD, Hallek M, O’Brien SM (2014) Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 370(11):997–1007. https://doi.org/10.1056/NEJMoa1315226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Talevi A (2015) Multi-target pharmacology: possibilities and limitations of the “skeleton key approach” from a medicinal chemist perspective. Front Pharmacol 6:205

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Verma R, Pinto SM, Patil AH, Advani J, Subba P, Kumar M et al (2017) Quantitative Proteomic and Phosphoproteomic Analysis of H37Ra and H37Rv Strains of Mycobacterium tuberculosis. J Proteome Res 16:1632–1645

    Article  CAS  PubMed  Google Scholar 

  54. Amanchy R, Zhong J, Hong R, Kim JH, Gucek M, Cole RN et al (2009) Identification of c-Src tyrosine kinase substrates in platelet-derived growth factor receptor signaling. Mol Oncol 3:439–450

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Amanchy R, Zhong J, Molina H, Chaerkady R, Iwahori A, Kalume DE et al (2008) Identification of c-Src tyrosine kinase substrates using mass spectrometry and peptide microarrays. J Proteome Res 7:3900–3910

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Harsha HC, Molina H, Pandey A (2008) Quantitative proteomics using stable isotope labeling with amino acids in cell culture. Nat Protoc 3:505–516

    Article  CAS  PubMed  Google Scholar 

  57. Ross PL, Huang YN, Marchese JN, Williamson B, Parker K, Hattan S et al (2004) Multiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagents. Mol Cell Proteomics 3:1154–1169

    Article  CAS  PubMed  Google Scholar 

  58. Thompson A, Schafer J, Kuhn K, Kienle S, Schwarz J, Schmidt G et al (2003) Tandem mass tags: a novel quantification strategy for comparative analysis of complex protein mixtures by MS/MS. Anal Chem 75:1895–1904

    Article  CAS  PubMed  Google Scholar 

  59. Frackelton AR Jr, Posner M, Kannan B, Mermelstein F (1991) Generation of monoclonal antibodies against phosphotyrosine and their use for affinity purification of phosphotyrosine-containing proteins. Methods Enzymol 201:79–92

    Article  CAS  PubMed  Google Scholar 

  60. Sathe G, Pinto SM, Syed N, Nanjappa V, Solanki HS, Renuse S et al (2016) Phosphotyrosine profiling of curcumin-induced signaling. Clin Proteomics 13:13

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Wu X, Zahari MS, Ma B, Liu R, Renuse S, Sahasrabuddhe NA et al (2015) Global phosphotyrosine survey in triple-negative breast cancer reveals activation of multiple tyrosine kinase signaling pathways. Oncotarget 6:29143–29160

    PubMed  PubMed Central  Google Scholar 

  62. Syed N, Barbhuiya MA, Pinto SM, Nirujogi RS, Renuse S, Datta KK et al (2015) Phosphotyrosine profiling identifies ephrin receptor A2 as a potential therapeutic target in esophageal squamous-cell carcinoma. Proteomics 15:374–382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Luo W, Slebos RJ, Hill S, Li M, Brabek J, Amanchy R et al (2008) Global impact of oncogenic Src on a phosphotyrosine proteome. J Proteome Res 7:3447–3460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Ibarrola N, Kratchmarova I, Nakajima D, Schiemann WP, Moustakas A, Pandey A et al (2004) Cloning of a novel signaling molecule, AMSH-2, that potentiates transforming growth factor beta signaling. BMC Cell Biol 5:2

    Article  PubMed  PubMed Central  Google Scholar 

  65. Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ et al (2005) Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat Biotechnol 23:94–101

    Article  CAS  PubMed  Google Scholar 

  66. Thingholm TE, Larsen MR (2016) Phosphopeptide enrichment by immobilized metal affinity chromatography. Methods Mol Biol 1355:123–133

    Article  CAS  PubMed  Google Scholar 

  67. Dunn JD, Reid GE, Bruening ML (2010) Techniques for phosphopeptide enrichment prior to analysis by mass spectrometry. Mass Spectrom Rev 29:29–54

    CAS  PubMed  Google Scholar 

  68. Selvan LDN, Danda R, Madugundu AK, Puttamallesh VN, Sathe GJ, Krishnan UM et al (2018) Phosphoproteomics of retinoblastoma: a pilot study identifies aberrant kinases. Molecules 23:E1454

    Article  PubMed  CAS  Google Scholar 

  69. Barua P, Lande NV, Subba P, Gayen D, Pinto S, Keshava Prasad TS et al (2019) Dehydration-responsive nuclear proteome landscape of chickpea (Cicer arietinum L.) reveals phosphorylation-mediated regulation of stress response. Plant Cell Environ 42:230

    Article  CAS  PubMed  Google Scholar 

  70. Gowthami N, Sunitha B, Kumar M, Keshava Prasad TS, Gayathri N, Padmanabhan B et al (2019) Mapping the protein phosphorylation sites in human mitochondrial complex I (NADH: Ubiquinone oxidoreductase): a bioinformatics study with implications for brain aging and neurodegeneration. J Chem Neuroanat 95:13

    Article  CAS  PubMed  Google Scholar 

  71. 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 6:1103–1109

    Article  CAS  PubMed  Google Scholar 

  72. Steen H, Mann M (2004) The ABC’s (and XYZ’s) of peptide sequencing. Nat Rev Mol Cell Biol 5:699–711

    Article  CAS  PubMed  Google Scholar 

  73. Nesvizhskii AI (2010) A survey of computational methods and error rate estimation procedures for peptide and protein identification in shotgun proteomics. J Proteomics 73:2092–2123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Chou MF, Schwartz D (2011) Biological sequence motif discovery using motif-x. Curr Protoc Bioinformatics Chapter 13:Unit 13:15–24

    PubMed  Google Scholar 

  75. Hansen AM, Chaerkady R, Sharma J, Diaz-Mejia JJ, Tyagi N, Renuse S et al (2013) The Escherichia coli phosphotyrosine proteome relates to core pathways and virulence. PLoS Pathog 9:e1003403

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Tan WL, Jain A, Takano A, Newell EW, Iyer NG, Lim WT et al (2016) Novel therapeutic targets on the horizon for lung cancer. Lancet Oncol 17:e347–e362

    Article  CAS  PubMed  Google Scholar 

  77. Eid S, Turk S, Volkamer A, Rippmann F, Fulle S (2017) KinMap: a web-based tool for interactive navigation through human kinome data. BMC Bioinformatics 18:16

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Feng X, Lu X, Man X, Zhou W, Jiang LQ, Knyazev P et al (2009) Overexpression of Csk-binding protein contributes to renal cell carcinogenesis. Oncogene 28:3320–3331

    Article  CAS  PubMed  Google Scholar 

  79. Kanehisa M, Goto S (2000) KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28:27–30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Fabregat A, Sidiropoulos K, Garapati P, Gillespie M, Hausmann K, Haw R et al (2016) The Reactome pathway Knowledgebase. Nucleic Acids Res 44:D481–D487

    Article  CAS  PubMed  Google Scholar 

  81. Kandasamy K, Mohan SS, Raju R, Keerthikumar S, Kumar GS, Venugopal AK et al (2010) NetPath: a public resource of curated signal transduction pathways. Genome Biol 11:R3

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Raju R, Nanjappa V, Balakrishnan L, Radhakrishnan A, Thomas JK, Sharma J et al (2011) NetSlim: high-confidence curated signaling maps. Database (Oxford) 2011:bar032

    Google Scholar 

  83. Kutmon M, Riutta A, Nunes N, Hanspers K, Willighagen EL, Bohler A et al (2016) WikiPathways: capturing the full diversity of pathway knowledge. Nucleic Acids Res 44:D488–D494

    Article  CAS  PubMed  Google Scholar 

  84. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D et al (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13:2498–2504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Zhong J, Kim MS, Chaerkady R, Wu X, Huang TC, Getnet D et al (2012) TSLP signaling network revealed by SILAC-based phosphoproteomics. Mol Cell Proteomics 11:M112 017764

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Zhong J, Sharma J, Raju R, Palapetta SM, Prasad TS, Huang TC et al (2014) TSLP signaling pathway map: a platform for analysis of TSLP-mediated signaling. Database (Oxford) 2014:bau007

    Article  CAS  Google Scholar 

  87. Pinto SM, Subbannayya Y, Rex DB, Raju R, Chatterjee O, Advani J et al (2018) A network map of IL-33 signaling pathway. J Cell Commun Signal 12:615–624

    Article  PubMed  PubMed Central  Google Scholar 

  88. Liu X, Zhu L, Lu X, Bian H, Wu X, Yang W et al (2014) IL-33/ST2 pathway contributes to metastasis of human colorectal cancer. Biochem Biophys Res Commun 453:486–492

    Article  CAS  PubMed  Google Scholar 

  89. Sharma K, D’souza RC, Tyanova S, Schaab C, Wisniewski JR, Cox J et al (2014) Ultradeep human phosphoproteome reveals a distinct regulatory nature of Tyr and Ser/Thr-based signaling. Cell Rep 8:1583–1594

    Article  CAS  PubMed  Google Scholar 

  90. Tyanova S, Cox J, Olsen J, Mann M, Frishman D (2013) Phosphorylation variation during the cell cycle scales with structural propensities of proteins. PLoS Comput Biol 9:e1002842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Beltrao P, Trinidad JC, Fiedler D, Roguev A, Lim WA, Shokat KM et al (2009) Evolution of phosphoregulation: comparison of phosphorylation patterns across yeast species. PLoS Biol 7:e1000134

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Ong SE, Blagoev B, Kratchmarova I, Kristensen DB, Steen H, Pandey A et al (2002) Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol Cell Proteomics 1:376–386

    Article  CAS  PubMed  Google Scholar 

  93. Amanchy R, Kalume DE, Pandey A (2005) Stable isotope labeling with amino acids in cell culture (SILAC) for studying dynamics of protein abundance and posttranslational modifications. Sci STKE 2005:pl2

    PubMed  Google Scholar 

  94. Wu CC, Maccoss MJ, Howell KE, Matthews DE, Yates JR III (2004) Metabolic labeling of mammalian organisms with stable isotopes for quantitative proteomic analysis. Anal Chem 76:4951–4959

    Article  CAS  PubMed  Google Scholar 

  95. Pierce A, Unwin RD, Evans CA, Griffiths S, Carney L, Zhang L et al (2008) Eight-channel iTRAQ enables comparison of the activity of six leukemogenic tyrosine kinases. Mol Cell Proteomics 7:853–863

    Article  CAS  PubMed  Google Scholar 

  96. Stepanova E, Gygi SP, Paulo JA (2018) Filter-based protein digestion (FPD): a detergent-free and scaffold-based strategy for TMT workflows. J Proteome Res 17:1227–1234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Stehelin D, Guntaka RV, Varmus HE, Bishop JM (1976) Purification of DNA complementary to nucleotide sequences required for neoplastic transformation of fibroblasts by avian sarcoma viruses. J Mol Biol 101:349–365

    Article  CAS  PubMed  Google Scholar 

  98. Spector DH, Varmus HE, Bishop JM (1978) Nucleotide sequences related to the transforming gene of avian sarcoma virus are present in DNA of uninfected vertebrates. Proc Natl Acad Sci U S A 75:4102–4106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Brugge JS, Erikson RL (1977) Identification of a transformation-specific antigen induced by an avian sarcoma virus. Nature 269:346–348

    Article  CAS  PubMed  Google Scholar 

  100. Hunter T, Sefton BM (1980) Transforming gene product of Rous sarcoma virus phosphorylates tyrosine. Proc Natl Acad Sci U S A 77:1311–1315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Wu P, Nielsen TE, Clausen MH (2015) FDA-approved small-molecule kinase inhibitors. Trends Pharmacol Sci 36:422–439

    Article  CAS  PubMed  Google Scholar 

  102. Fabbro D, Cowan-Jacob SW, Moebitz H (2015) Ten things you should know about protein kinases: IUPHAR review 14. Br J Pharmacol 172:2675–2700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Demir E, Cary MP, Paley S, Fukuda K, Lemer C, Vastrik I et al (2010) The BioPAX community standard for pathway data sharing. Nat Biotechnol 28:935–942

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Hucka M, Finney A, Sauro HM, Bolouri H, Doyle JC, Kitano H et al (2003) The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models. Bioinformatics 19:524–531

    Article  CAS  PubMed  Google Scholar 

  105. Hermjakob H, Montecchi-Palazzi L, Bader G, Wojcik J, Salwinski L, Ceol A et al (2004) The HUPO PSI’s molecular interaction format--a community standard for the representation of protein interaction data. Nat Biotechnol 22:177–183

    Article  CAS  PubMed  Google Scholar 

  106. Van Iersel MP, Kelder T, Pico AR, Hanspers K, Coort S, Conklin BR et al (2008) Presenting and exploring biological pathways with PathVisio. BMC Bioinformatics 9:399

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  107. Keshava Prasad TS, Goel R, Kandasamy K, Keerthikumar S, Kumar S, Mathivanan S et al (2009) Human protein reference database--2009 update. Nucleic Acids Res 37:D767–D772

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

PK is a recipient of the Ramanujan Fellowship awarded by Department of Science and Technology (DST), Government of India. BD is a recipient of INSPIRE Fellowship from Department of Science and Technology (DST), Government of India. IAG is a recipient of junior research fellowship from Council of Scientific and Industrial Research (CSIR), Government of India. JS is a recipient of Bio-CARe Women Scientists award conferred by Department of Biotechnology (DBT), Government of India.

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Deb, B., George, I.A., Sharma, J., Kumar, P. (2020). Phosphoproteomics Profiling to Identify Altered Signaling Pathways and Kinase-Targeted Cancer Therapies. In: Matthiesen, R. (eds) Mass Spectrometry Data Analysis in Proteomics. Methods in Molecular Biology, vol 2051. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9744-2_10

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  • DOI: https://doi.org/10.1007/978-1-4939-9744-2_10

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9743-5

  • Online ISBN: 978-1-4939-9744-2

  • eBook Packages: Springer Protocols

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