TSLP signaling network revealed by SILAC-based phosphoproteomics

Molecular and Cellular Proteomics

Volumn 11, Issue 6, 2012, Pages

  Zhong, Jun ^a   Kim, Min Sik ^a   Chaerkady, Raghothama ^a,b   Wu, Xinyan ^a   Huang, Tai Chung ^a   Getnet, Derese ^a   Mitchell, Christopher J ^a   Palapetta, Shyam M ^b,c   Sharma, Jyoti ^b,d   O'Meally, Robert N ^a   Cole, Robert N ^a   Yoda, Akinori ^e   Moritz, Albrecht ^f   Loriaux, Marc M ^g   Rush, John ^f   Weinstock, David M ^e   Tyner, Jeffrey W ^h   Pandey, Akhilesh ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b Institute of Bioinformatics   (India)

^c PONDICHERRY UNIVERSITY   (India)

^d MANIPAL UNIVERSITY   (India)

^e HARVARD MEDICAL SCHOOL   (United States)

^f CELL SIGNALING TECHNOLOGY   (United States)

^g OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^h OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBODY; BRUTON TYROSINE KINASE; JANUS KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHOPROTEIN PHOSPHATASE; PHOSPHOTYROSINE ANTIBODY; PROTEIN; PROTEIN GAB2; PROTEIN KINASE INHIBITOR; PROTEIN KINASE LYN; PROTEIN SRC; PROTEIN TEC; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE PHOSPHATASE SHP 1; PROTEIN TYROSINE PHOSPHATASE SHP 2; THYMIC STROMAL LYMPHOPOIETIN; TITANIUM DIOXIDE; UNCLASSIFIED DRUG; CYTOKINE; PHOSPHOPROTEIN; PROTEIN KINASE; PROTEOME; SIGNAL PEPTIDE; STAT3 PROTEIN; STAT3 PROTEIN, MOUSE; STAT5 PROTEIN; STAT5A PROTEIN, MOUSE;

ARTICLE; CONTROLLED STUDY; HUMAN; IMMUNOPRECIPITATION; ISOTOPE LABELING; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN FAMILY; PROTEIN PHOSPHORYLATION; PROTEOMICS; QUANTITATIVE ANALYSIS; SIGNAL TRANSDUCTION; ANIMAL; CELL LINE; CELL PROLIFERATION; DRUG EFFECT; METABOLISM; MOUSE; PHOSPHORYLATION; PHYSIOLOGY; PROTEIN BINDING; PROTEIN MOTIF; PROTEIN PROCESSING; PROTEIN PROTEIN INTERACTION;

AMINO ACID MOTIFS; ANIMALS; CELL LINE; CELL PROLIFERATION; CYTOKINES; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; ISOTOPE LABELING; MICE; PHOSPHOPROTEIN PHOSPHATASES; PHOSPHOPROTEINS; PHOSPHORYLATION; PROTEIN BINDING; PROTEIN INTERACTION MAPS; PROTEIN KINASE INHIBITORS; PROTEIN KINASES; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEOME; SIGNAL TRANSDUCTION; STAT3 TRANSCRIPTION FACTOR; STAT5 TRANSCRIPTION FACTOR;

EID: 84862317369     PISSN: 15359476     EISSN: 15359484     Source Type: Journal    
DOI: 10.1074/mcp.M112.017764     Document Type: Article

References (142)

1. Friend, S. L., Hosier, S., Nelson, A., Foxworthe, D., Williams, D. E., and Farr, A. (1994) A thymic stromal cell line supports in vitro development of surface IgM+ B cells and produces a novel growth factor affecting B and T lineage cells. Exp. Hematol. 22, 321-328
2. Levin, S. D., Koelling, R. M., Friend, S. L., Isaksen, D. E., Ziegler, S. F., Perlmutter, R. M., and Farr, A. G. (1999) Thymic stromal lymphopoietin: a cytokine that promotes the development of IgM+ B cells in vitro and signals via a novel mechanism. J. Immunol. 162, 677-683
3. Pandey, A., Ozaki, K., Baumann, H., Levin, S. D., Puel, A., Farr, A. G., Ziegler, S. F., Leonard, W. J., and Lodish, H. F. (2000) Cloning of a receptor subunit required for signaling by thymic stromal lymphopoietin. Nat. Immunol. 1, 59-64
4. Park, L. S., Martin, U., Garka, K., Gliniak, B., Di Santo, J. P., Muller, W., Largaespada, D. A., Copeland, N. G., Jenkins, N. A., Farr, A. G., Ziegler, S. F., Morrissey, P. J., Paxton, R., and Sims, J. E. (2000) Cloning of the murine thymic stromal lymphopoietin (TSLP) receptor: Formation of a functional heteromeric complex requires interleukin 7 receptor. J. Exp. Med. 192, 659-670
5. Soumelis, V., Reche, P. A., Kanzler, H., Yuan, W., Edward, G., Homey, B., Gilliet, M., Ho, S., Antonenko, S., Lauerma, A., Smith, K., Gorman, D., Zurawski, S., Abrams, J., Menon, S., McClanahan, T., de Waal-Malefyt Rd, R., Bazan, F., Kastelein, R. A., and Liu, Y. J. (2002) Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat. Immunol. 3, 673-680
6. Allakhverdi, Z., Comeau, M. R., Jessup, H. K., Yoon, B. R., Brewer, A., Chartier, S., Paquette, N., Ziegler, S. F., Sarfati, M., and Delespesse, G. (2007) Thymic stromal lymphopoietin is released by human epithelial cells in response to microbes, trauma, or inflammation and potently activates mast cells. J. Exp. Med. 204, 253-258
7. Liu, Y. J., Soumelis, V., Watanabe, N., Ito, T., Wang, Y. H., Malefyt Rde, W., Omori, M., Zhou, B., and Ziegler, S. F. (2007) TSLP: an epithelial cell cytokine that regulates T cell differentiation by conditioning dendritic cell maturation. Annu. Rev. Immunol. 25, 193-219
8. Akamatsu, T., Watanabe, N., Kido, M., Saga, K., Tanaka, J., Kuzushima, K., Nishio, A., and Chiba, T. (2008) Human TSLP directly enhances expansion of CD8+ T cells. Clin. Exp. Immunol. 154, 98-106
9. Rochman, I., Watanabe, N., Arima, K., Liu, Y. J., and Leonard, W. J. (2007) Cutting edge: direct action of thymic stromal lymphopoietin on activated human CD4+ T cells. J. Immunol. 178, 6720-6724
10. Zhou, B., Comeau, M. R., De Smedt, T., Liggitt, H. D., Dahl, M. E., Lewis, D. B., Gyarmati, D., Aye, T., Campbell, D. J., and Ziegler, S. F. (2005) Thymic stromal lymphopoietin as a key initiator of allergic airway inflammation in mice. Nat. Immunol. 6, 1047-1053
11. Omori, M., and Ziegler, S. (2007) Induction of IL-4 expression in CD4(+) T cells by thymic stromal lymphopoietin. J. Immunol. 178, 1396-1404
12. Rochman, Y., and Leonard, W. J. (2008) The role of thymic stromal lymphopoietin in CD8+ T cell homeostasis. J. Immunol. 181, 7699-7705
13. Scheeren, F. A., van Lent, A. U., Nagasawa, M., Weijer, K., Spits, H., Legrand, N., and Blom, B. (2010) Thymic stromal lymphopoietin induces early human B-cell proliferation and differentiation. Eur. J. Immunol. 40, 955-965
14. Ying, S., O'Connor, B., Ratoff, J., Meng, Q., Mallett, K., Cousins, D., Robinson, D., Zhang, G., Zhao, J., Lee, T. H., and Corrigan, C. (2005) Thymic stromal lymphopoietin expression is increased in asthmatic airways and correlates with expression of Th2-attracting chemokines and disease severity. J. Immunol. 174, 8183-8190
15. Ying, S., O'Connor, B., Ratoff, J., Meng, Q., Fang, C., Cousins, D., Zhang, G., Gu, S., Gao, Z., Shamji, B., Edwards, M. J., Lee, T. H., and Corrigan, C. J. (2008) Expression and cellular provenance of thymic stromal lymphopoietin and chemokines in patients with severe asthma and chronic obstructive pulmonary disease. J. Immunol. 181, 2790-2798
16. Al-Shami, A., Spolski, R., Kelly, J., Keane-Myers, A., and Leonard, W. J. (2005) A role for TSLP in the development of inflammation in an asthma model. J. Exp. Med. 202, 829-839
17. Headley, M. B., Zhou, B., Shih, W. X., Aye, T., Comeau, M. R., and Ziegler, S. F. (2009) TSLP Conditions the Lung Immune Environment for the Generation of Pathogenic Innate and Antigen-Specific Adaptive Immune Responses. J. Immunol. 182, 1641-1647
18. Yoo, J., Omori, M., Gyarmati, D., Zhou, B., Aye, T., Brewer, A., Comeau, M. R., Campbell, D. J., and Ziegler, S. F. (2005) Spontaneous atopic dermatitis in mice expressing an inducible thymic stromal lymphopoietin transgene specifically in the skin. J. Exp. Med. 202, 541-549
19. Zhang, Z., Hener, P., Frossard, N., Kato, S., Metzger, D., Li, M., and Chambon, P. (2009) Thymic stromal lymphopoietin overproduced by keratinocytes in mouse skin aggravates experimental asthma. Proc. Natl. Acad. Sci. U.S.A. 106, 1536-1541
20. Rothenberg, M. E., Spergel, J. M., Sherrill, J. D., Annaiah, K., Martin, L. J., Cianferoni, A., Gober, L., Kim, C., Glessner, J., Frackelton, E., Thomas, K., Blanchard, C., Liacouras, C., Verma, R., Aceves, S., Collins, M. H., Brown-Whitehorn, T., Putnam, P. E., Franciosi, J. P., Chiavacci, R. M., Grant, S. F., Abonia, J. P., Sleiman, P. M., and Hakonarson, H. (2010) Common variants at 5q22 associate with pediatric eosinophilic esophagitis. Nat. Genet. 42, 289-291
21. Cario, G., Zimmermann, M., Romey, R., Gesk, S., Vater, I., Harbott, J., Schrauder, A., Moericke, A., Izraeli, S., Akasaka, T., Dyer, M. J., Siebert, R., Schrappe, M., and Stanulla, M. (2010) Presence of the P2RY8- CRLF2 rearrangement is associated with a poor prognosis in non-highrisk precursor B-cell acute lymphoblastic leukemia in children treated according to the ALL-BFM 2000 protocol. Blood 115, 5393-5397
22. Tsai, A. G., Yoda, A., Weinstock, D. M., and Lieber, M. R. (2010) t(X; 14)(p22;q32)/t(Y;14)(p11;q32) CRLF2-IGH translocations from human B-lineage ALLs involve CpG-type breaks at CRLF2, but CRLF2/P2RY8 intrachromosomal deletions do not. Blood 116, 1993-1994
23. Chapiro, E., Russell, L., Lainey, E., Kaltenbach, S., Ragu, C., Della-Valle, V., Hanssens, K., Macintyre, E. A., Radford-Weiss, I., Delabesse, E., Cavé , H., Mercher, T., Harrison, C. J., Nguyen-Khac, F., Dubreuil, P., and Bernard, O. A. (2010) Activating mutation in the TSLPR gene in B-cell precursor lymphoblastic leukemia. Leukemia 24, 642-645
24. Dyer, M. J., Akasaka, T., Capasso, M., Dusanjh, P., Lee, Y. F., Karran, E.L., Nagel, I., Vater, I., Cario, G., and Siebert, R. (2010) Immunoglobulin heavy chain locus chromosomal translocations in B-cell precursor acute lymphoblastic leukemia: rare clinical curios or potent genetic drivers? Blood 115, 1490-1499
25. Hertzberg, L., Vendramini, E., Ganmore, I., Cazzaniga, G., Schmitz, M., Chalker, J., Shiloh, R., Iacobucci, I., Shochat, C., Zeligson, S., Cario, G., Stanulla, M., Strehl, S., Russell, L. J., Harrison, C. J., Bornhauser, B., Yoda, A., Rechavi, G., Bercovich, D., Borkhardt, A., Kempski, H., te Kronnie, G., Bourquin, J. P., Domany, E., and Izraeli, S. (2010) Down syndrome acute lymphoblastic leukemia, a highly heterogeneous disease in which aberrant expression of CRLF2 is associated with mutated JAK2: a report from the International BFM Study Group. Blood 115, 1006-1017
26. Yoda, A., Yoda, Y., Chiaretti, S., Bar-Natan, M., Mani, K., Rodig, S.J., West, N., Xiao, Y., Brown, J. R., Mitsiades, C., Sattler, M., Kutok, J. L., DeAngelo, D. J., Wadleigh, M., Piciocchi, A., Dal Cin, P., Bradner, J. E., Griffin, J. D., Anderson, K. C., Stone, R. M., Ritz, J., Foà, R., Aster, J. C., Frank, D. A., and Weinstock, D. M. (2010) Functional screening identifies CRLF2 in precursor B-cell acute lymphoblastic leukemia. Proc. Natl. Acad. Sci. U.S.A. 107, 252-257
27. Russell, L. J., Capasso, M., Vater, I., Akasaka, T., Bernard, O. A., Calasanz, M. J., Chandrasekaran, T., Chapiro, E., Gesk, S., Griffiths, M., Guttery, D. S., Haferlach, C., Harder, L., Heidenreich, O., Irving, J., Kearney, L., Nguyen-Khac, F., Machado, L., Minto, L., Majid, A., Moorman, A. V., Morrison, H., Rand, V., Strefford, J. C., Schwab, C., Tönnies, H., Dyer, M. J., Siebert, R., and Harrison, C. J. (2009) Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia. Blood 114, 2688-2698
28. Mullighan, C. G., Collins-Underwood, J. R., Phillips, L. A., Loudin, M. G., Liu, W., Zhang, J., Ma, J., Coustan-Smith, E., Harvey, R. C., Willman, C. L., Mikhail, F. M., Meyer, J., Carroll, A. J., Williams, R. T., Cheng, J., Heerema, N. A., Basso, G., Pession, A., Pui, C. H., Raimondi, S. C., Hunger, S. P., Downing, J. R., Carroll, W. L., and Rabin, K. R. (2009) Rearrangement of CRLF2 in B-progenitor- and Down syndrome-associated acute lymphoblastic leukemia. Nat. Genet. 41, 1243-1246
29. Arima, K., Watanabe, N., Hanabuchi, S., Chang, M., Sun, S. C., and Liu, Y. J. (2010) Distinct signal codes generate dendritic cell functional plasticity. Sci. Signal. 3, ra4
30. Wohlmann, A., Sebastian, K., Borowski, A., Krause, S., and Friedrich, K. (2010) Signal transduction by the atopy-associated human thymic stromal lymphopoietin (TSLP) receptor depends on Janus kinase function. Biol. Chem. 391, 181-186
31. Rochman, Y., Kashyap, M., Robinson, G. W., Sakamoto, K., Gomez- Rodriguez, J., Wagner, K. U., and Leonard, W. J. (2010) Thymic stromal lymphopoietin-mediated STAT5 phosphorylation via kinases JAK1 and JAK2 reveals a key difference from IL-7-induced signaling. Proc. Natl. Acad. Sci. U.S.A. 107, 19455-19460
32. Shan, L., Redhu, N. S., Saleh, A., Halayko, A. J., Chakir, J., and Gounni, A. S. (2010) Thymic stromal lymphopoietin receptor-mediated IL-6 and CC/CXC chemokines expression in human airway smooth muscle cells: role of MAPKs (ERK1/2, p38, and JNK) and STAT3 pathways. J. Immunol. 184, 7134-7143
33. Brown, V. I., Hulitt, J., Fish, J., Sheen, C., Bruno, M., Xu, Q., Carroll, M., Fang, J., Teachey, D., and Grupp, S. A. (2007) Thymic stromal-derived lymphopoietin induces proliferation of pre-B leukemia and antagonizes mTOR inhibitors, suggesting a role for interleukin-7Ralpha signaling. Cancer Res. 67, 9963-9970
34. Ong, S. E., Blagoev, B., Kratchmarova, I., Kristensen, D. B., Steen, H., Pandey, A., and 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, 376-386
35. Harsha, H. C., Molina, H., and Pandey, A. (2008) Quantitative proteomics using stable isotope labeling with amino acids in cell culture. Nat. Protoc. 3, 505-516
36. Mann, M. (2006) Functional and quantitative proteomics using SILAC. Nat. Rev. Mol. Cell Biol. 7, 952-958
37. Ibarrola, N., Kalume, D. E., Gronborg, M., Iwahori, A., and Pandey, A. (2003) A proteomic approach for quantitation of phosphorylation using stable isotope labeling in cell culture. Anal. Chem. 75, 6043-6049
38. Blagoev, B., Ong, S. E., Kratchmarova, I., and Mann, M. (2004) Temporal analysis of phosphotyrosine-dependent signaling networks by quantitative proteomics. Nat. Biotechnol. 22, 1139-1145
39. Zhang, G., Spellman, D. S., Skolnik, E. Y., and Neubert, T. A. (2006) Quantitative phosphotyrosine proteomics of EphB2 signaling by stable isotope labeling with amino acids in cell culture (SILAC). J. Proteome Res. 5, 581-588
40. Bose, R., Molina, H., Patterson, A. S., Bitok, J. K., Periaswamy, B., Bader, J. S., Pandey, A., and Cole, P. A. (2006) Phosphoproteomic analysis of Her2/neu signaling and inhibition. Proc. Natl. Acad. Sci. U.S.A. 103, 9773-9778
41. Amanchy, R., Zhong, J., Hong, R., Kim, J. H., Gucek, M., Cole, R. N., Molina, H., and Pandey, A. (2009) Identification of c-Src tyrosine kinase substrates in platelet-derived growth factor receptor signaling. Mol. Oncol. 3, 439-450
42. Kratchmarova, I., Blagoev, B., Haack-Sorensen, M., Kassem, M., and Mann, M. (2005) Mechanism of divergent growth factor effects in mesenchymal stem cell differentiation. Science 308, 1472-1477
43. Pandey, A., Podtelejnikov, A. V., Blagoev, B., Bustelo, X. R., Mann, M., and Lodish, H. F. (2000) Analysis of receptor signaling pathways by mass spectrometry: identification of vav-2 as a substrate of the epidermal and platelet-derived growth factor receptors. Proc. Natl. Acad. Sci. U.S.A. 97, 179-184
44. Posewitz, M. C., and Tempst, P. (1999) Immobilized gallium(III) affinity chromatography of phosphopeptides. Anal. Chem. 71, 2883-2892
45. Ficarro, S. B., McCleland, M. L., Stukenberg, P. T., Burke, D. J., Ross, M. M., Shabanowitz, J., Hunt, D. F., and White, F. M. (2002) Phosphoproteome analysis by mass spectrometry and its application to Saccharomyces cerevisiae. Nat. Biotechnol. 20, 301-305
46. 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
47. Kuroda, I., Shintani, Y., Motokawa, M., Abe, S., and Furuno, M. (2004) Phosphopeptide-selective column-switching RP-HPLC with a titania precolumn. Anal. Sci. 20, 1313-1319
48. Ballif, B. A., Villé n, J., Beausoleil, S. A., Schwartz, D., and Gygi, S. P. (2004) Phosphoproteomic analysis of the developing mouse brain. Mol. Cell. Proteomics 3, 1093-1101
49. Beausoleil, S. A., Jedrychowski, M., Schwartz, D., Elias, J. E., Villé n, J., Li, J., Cohn, M. A., Cantley, L. C., and Gygi, S. P. (2004) Large-scale characterization of HeLa cell nuclear phosphoproteins. Proc. Natl. Acad. Sci. U.S.A. 101, 12130-12135
50. 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
51. Gruhler, A., Olsen, J. V., Mohammed, S., Mortensen, P., Faergeman, N. J., Mann, M., and Jensen, O. N. (2005) Quantitative phosphoproteomics applied to the yeast pheromone signaling pathway. Mol. Cell. Proteomics 4, 310-327
52. Nguyen, V., Cao, L., Lin, J. T., Hung, N., Ritz, A., Yu, K., Jianu, R., Ulin, S. P., Raphael, B. J., Laidlaw, D. H., Brossay, L., and Salomon, A. R. (2009) A new approach for quantitative phosphoproteomic dissection of signaling pathways applied to T cell receptor activation. Mol. Cell. Proteomics 8, 2418-2431
53. 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
54. 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
55. 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., and Varmus, H. E. (2008) Comparisons of tyrosine phosphorylated proteins in cells expressing lung cancer-specific alleles of EGFR and KRAS. Proc. Natl. Acad. Sci. U.S.A. 105, 14112-14117
56. Rubbi, L., Titz, B., Brown, L., Galvan, E., Komisopoulou, E., Chen, S.S., Low, T., Tahmasian, M., Skaggs, B., Müschen, M., Pellegrini, M., and Graeber, T. G. (2011) Global phosphoproteomics reveals crosstalk between bcr-abl and negative feedback mechanisms controlling SRC signaling. Sci. Signal. 4, ra18
57. Zhong, J., and Pandey, A. (2010) Site-directed mutagenesis reveals a unique requirement for tyrosine residues in IL-7R alpha and TSLPR cytoplasmic domains in TSLP-dependent cell proliferation. BMC Immunol. 11, 5
58. Perkins, D. N., Pappin, D. J., Creasy, D. M., and Cottrell, J. S. (1999) Probability-based protein identification by searching sequence databases using mass spectrometry data. Electrophoresis 20, 3551-3567
59. Eng, J. K., Mccormack, A. L., and 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, 976-989
60. Schwartz, D., and Gygi, S. P. (2005) An iterative statistical approach to the identification of protein phosphorylation motifs from large-scale data sets. Nat. Biotechnol. 23, 1391-1398
61. Mi, H., Dong, Q., Muruganujan, A., Gaudet, P., Lewis, S., and Thomas, P. D. (2010) PANTHER version 7: improved phylogenetic trees, orthologs and collaboration with the Gene Ontology Consortium. Nucleic Acids Res. 38, D204-210
62. Molina, H., Horn, D. M., Tang, N., Mathivanan, S., and Pandey, A. (2007) Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry. Proc. Natl. Acad. Sci. U.S.A. 104, 2199-2204
63. Isaksen, D. E., Baumann, H., Trobridge, P. A., Farr, A. G., Levin, S. D., and Ziegler, S. F. (1999) Requirement for stat5 in thymic stromal lympho-poietin- mediated signal transduction. J. Immunol. 163, 5971-5977
64. Rawlings, D. J., and Witte, O. N. (1994) Bruton's tyrosine kinase is a key regulator in B-cell development. Immunol. Rev. 138, 105-119
65. Rawlings, D. J., Scharenberg, A. M., Park, H., Wahl, M. I., Lin, S., Kato, R. M., Fluckiger, A. C., Witte, O. N., and Kinet, J. P. (1996) Activation of BTK by a phosphorylation mechanism initiated by SRC family kinases. Science 271, 822-825
66. Katagiri, T., Ogimoto, M., Hasegawa, K., Arimura, Y., Mitomo, K., Okada, M., Clark, M. R., Mizuno, K., and Yakura, H. (1999) CD45 negatively regulates lyn activity by dephosphorylating both positive and negative regulatory tyrosine residues in immature B cells. J. Immunol. 163, 1321-1326
67. Somani, A. K., Yuen, K., Xu, F., Zhang, J., Branch, D. R., and Siminovitch, K. A. (2001) The SH2 domain containing tyrosine phosphatase-1 downregulates activation of Lyn and Lyn-induced tyrosine phosphorylation of the CD19 receptor in B cells. J. Biol. Chem. 276, 1938-1944
68. Greer, P. (2002) Closing in on the biological functions of Fps/Fes and Fer. Nat. Rev. Mol. Cell Biol. 3, 278-289
69. Hjermstad, S. J., Peters, K. L., Briggs, S. D., Glazer, R. I., and Smithgall, T. E. (1993) Regulation of the human c-fes protein tyrosine kinase (p93c-fes) by its src homology 2 domain and major autophosphorylation site (Tyr-713). Oncogene 8, 2283-2292
70. Rogers, J. A., Read, R. D., Li, J., Peters, K. L., and Smithgall, T. E. (1996) Autophosphorylation of the Fes tyrosine kinase. Evidence for an intermolecular mechanism involving two kinase domain tyrosine residues. J. Biol. Chem. 271, 17519-17525
71. Reinhardt, H. C., and Yaffe, M. B. (2009) Kinases that control the cell cycle in response to DNA damage: Chk1, Chk2, and MK2. Curr. Opin. Cell Biol. 21, 245-255
72. Walter, S. A., Cutler, R. E., Jr., Martinez, R., Gishizky, M., and Hill, R. J. (2003) Stk10, a new member of the polo-like kinase kinase family highly expressed in hematopoietic tissue. J. Biol. Chem. 278, 18221-18228
73. Yi, T., Cleveland, J. L., and Ihle, J. N. (1991) Identification of novel protein tyrosine phosphatases of hematopoietic cells by polymerase chain reaction amplification. Blood 78, 2222-2228
74. Klingmüller, U., Lorenz, U., Cantley, L. C., Neel, B. G., and Lodish, H. F. (1995) Specific recruitment of SH-PTP1 to the erythropoietin receptor causes inactivation of JAK2 and termination of proliferative signals. Cell 80, 729-738
75. Shultz, L. D., Schweitzer, P. A., Rajan, T. V., Yi, T., Ihle, J. N., Matthews, R.J., Thomas, M. L., and Beier, D. R. (1993) Mutations at the murine motheaten locus are within the hematopoietic cell protein-tyrosine phosphatase (Hcph) gene. Cell 73, 1445-1454
76. Tsui, H. W., Siminovitch, K. A., de Souza, L., and Tsui, F. W. (1993) Motheaten and viable motheaten mice have mutations in the haematopoietic cell phosphatase gene. Nat. Genet. 4, 124-129
77. Zhang, Z., Shen, K., Lu, W., and Cole, P. A. (2003) The role of C-terminal tyrosine phosphorylation in the regulation of SHP-1 explored via expressed protein ligation. J. Biol. Chem. 278, 4668-4674
78. Uchida, T., Matozaki, T., Noguchi, T., Yamao, T., Horita, K., Suzuki, T., Fujioka, Y., Sakamoto, C., and Kasuga, M. (1994) Insulin stimulates the phosphorylation of Tyr538 and the catalytic activity of PTP1C, a protein tyrosine phosphatase with Src homology-2 domains. J. Biol. Chem. 269, 12220-12228
79. Cheng, J., Daimaru, L., Fennie, C., and Lasky, L. A. (1996) A novel protein tyrosine phosphatase expressed in lin(lo)CD34(hi)Sca(hi) hematopoietic progenitor cells. Blood 88, 1156-1167
80. Dosil, M., Leibman, N., and Lemischka, I. R. (1996) Cloning and characterization of fetal liver phosphatase 1, a nuclear protein tyrosine phosphatase isolated from hematopoietic stem cells. Blood 88, 4510-4525
81. Gensler, M., Buschbeck, M., and Ullrich, A. (2004) Negative regulation of HER2 signaling by the PEST-type protein-tyrosine phosphatase BDP1. J. Biol. Chem. 279, 12110-12116
82. Barylko, B., Gerber, S. H., Binns, D. D., Grichine, N., Khvotchev, M., Südhof, T. C., and Albanesi, J. P. (2001) A novel family of phosphatidylinositol 4-kinases conserved from yeast to humans. J. Biol. Chem. 276, 7705-7708
83. Huber, M., Helgason, C. D., Damen, J. E., Scheid, M., Duronio, V., Liu, L., Ware, M. D., Humphries, R. K., and Krystal, G. (1999) The role of SHIP in growth factor induced signalling. Prog. Biophys. Mol. Biol. 71, 423-434
84. Neel, B. G., Gu, H., and Pao, L. (2003) The 'Shp'ing news: SH2 domain-containing tyrosine phosphatases in cell signaling. Trends Biochem. Sci 28, 284-293
85. Neel, B. G., Gu, H., and Pao, L. (2003) SH2 domain-containing proteintyrosine phosphatases. in Handbook of Cell Signaling, ed.R. Bradshaw and E. Dennis, pp. 707-730. London: Elsevier
86. Uhlé n, P., Burch, P. M., Zito, C. I., Estrada, M., Ehrlich, B. E., and Bennett, A. M. (2006) Gain-of-function/Noonan syndrome SHP-2/Ptpn11 mutants enhance calcium oscillations and impair NFAT signaling. Proc. Natl. Acad. Sci. U.S.A. 103, 2160-2165
87. Chan, G., Kalaitzidis, D., and Neel, B. G. (2008) The tyrosine phosphatase Shp2 (PTPN11) in cancer. Cancer Metastasis Rev 27, 179-192
88. Sattler, M., Mohi, M. G., Pride, Y. B., Quinnan, L. R., Malouf, N. A., Podar, K., Gesbert, F., Iwasaki, H., Li, S., Van Etten, R. A., Gu, H., Griffin, J. D., and Neel, B. G. (2002) Critical role for Gab2 in transformation by BCR/ABL. Cancer Cell 1, 479-492
89. Pan, Z., Scheerens, H., Li, S. J., Schultz, B. E., Sprengeler, P. A., Burrill, L. C., Mendonca, R. V., Sweeney, M. D., Scott, K. C., Grothaus, P. G., Jeffery, D. A., Spoerke, J. M., Honigberg, L. A., Young, P. R., Dalrymple, S. A., and Palmer, J. T. (2007) Discovery of selective irreversible inhibitors for Bruton's tyrosine kinase. ChemMedChem 2, 58-61
90. Davis, R. E., Ngo, V. N., Lenz, G., Tolar, P., Young, R. M., Romesser, P. B., Kohlhammer, H., Lamy, L., Zhao, H., Yang, Y., Xu, W., Shaffer, A. L., Wright, G., Xiao, W., Powell, J., Jiang, J. K., Thomas, C. J., Rosenwald, A., Ott, G., Muller-Hermelink, H. K., Gascoyne, R. D., Connors, J. M., Johnson, N. A., Rimsza, L. M., Campo, E., Jaffe, E. S., Wilson, W. H., Delabie, J., Smeland, E. B., Fisher, R. I., Braziel, R. M., Tubbs, R. R., Cook, J. R., Weisenburger, D. D., Chan, W. C., Pierce, S. K., and Staudt, L. M. (2010) Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature 463, 88-92
91. Herman, S. E., Gordon, A. L., Hertlein, E., Ramanunni, A., Zhang, X., Jaglowski, S., Flynn, J., Jones, J., Blum, K. A., Buggy, J. J., Hamdy, A., Johnson, A. J., and Byrd, J. C. (2011) Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. Blood 117, 6287-6296
92. Mahajan, S., Ghosh, S., Sudbeck, E. A., Zheng, Y., Downs, S., Hupke, M., and Uckun, F. M. (1999) Rational design and synthesis of a novel anti-leukemic agent targeting Bruton's tyrosine kinase (BTK), LFM-A13 [alpha-cyano-beta- hydroxy-beta-methyl-N-(2, 5-dibromophenyl)propenamide]. J. Biol. Chem. 274, 9587-9599
93. Harvey, R. C., Mullighan, C. G., Chen, I. M., Wharton, W., Mikhail, F. M., Carroll, A. J., Kang, H., Liu, W., Dobbin, K. K., Smith, M. A., Carroll, W. L., Devidas, M., Bowman, W. P., Camitta, B. M., Reaman, G. H., Hunger, S. P., Downing, J. R., and Willman, C. L. (2010) Rearrangement of CRLF2 is associated with mutation of JAK kinases, alteration of IKZF1, Hispanic/Latino ethnicity, and a poor outcome in pediatric Bprogenitor acute lymphoblastic leukemia. Blood 115, 5312-5321
94. Grønborg, M., Kristiansen, T. Z., Stensballe, A., Andersen, J. S., Ohara, O., Mann, M., Jensen, O. N., and Pandey, A. (2002) A mass spectrometrybased proteomic approach for identification of serine/threonine- phosphorylated proteins by enrichment with phospho-specific antibodies: identification of a novel protein, Frigg, as a protein kinase A substrate. Mol. Cell. Proteomics 1, 517-527
95. Quentmeier, H., Drexler, H. G., Fleckenstein, D., Zaborski, M., Armstrong, A., Sims, J. E., and Lyman, S. D. (2001) Cloning of human thymic stromal lymphopoietin (TSLP) and signaling mechanisms leading to proliferation. Leukemia 15, 1286-1292
96. Kandasamy, K., Mohan, S. S., Raju, R., Keerthikumar, S., Kumar, G. S., Venugopal, A. K., Telikicherla, D., Navarro, J. D., Mathivanan, S., Pecquet, C., Gollapudi, S. K., Tattikota, S. G., Mohan, S., Padhukasahasram, H., Subbannayya, Y., Goel, R., Jacob, H. K., Zhong, J., Sekhar, R., Nanjappa, V., Balakrishnan, L., Subbaiah, R., Ramachandra, Y. L., Rahiman, B. A., Prasad, T. S., Lin, J. X., Houtman, J. C., Desiderio, S., Renauld, J. C., Constantinescu, S. N., Ohara, O., Hirano, T., Kubo, M., Singh, S., Khatri, P., Draghici, S., Bader, G. D., Sander, C., Leonard, W. J., and Pandey, A. (2010) NetPath: a public resource of curated signal transduction pathways. Genome Biol. 11, R3
97. Raynaud, F. I., Eccles, S., Clarke, P. A., Hayes, A., Nutley, B., Alix, S., Henley, A., Di-Stefano, F., Ahmad, Z., Guillard, S., Bjerke, L. M., Kelland, L., Valenti, M., Patterson, L., Gowan, S., de Haven Brandon, A., Hayakawa, M., Kaizawa, H., Koizumi, T., Ohishi, T., Patel, S., Saghir, N., Parker, P., Waterfield, M., and Workman, P. (2007) Pharmacologic characterization of a potent inhibitor of class I phosphatidylinositide 3-kinases. Cancer Res. 67, 5840-5850
98. Park, S., Chapuis, N., Bardet, V., Tamburini, J., Gallay, N., Willems, L., Knight, Z. A., Shokat, K. M., Azar, N., Viguié , F., Ifrah, N., Dreyfus, F., Mayeux, P., Lacombe, C., and Bouscary, D. (2008) PI-103, a dual inhibitor of Class IA phosphatidylinositide 3-kinase and mTOR, has antileukemic activity in AML. Leukemia 22, 1698-1706
99. Ioannidis, S., Lamb, M. L., Wang, T., Almeida, L., Block, M. H., Davies, A. M., Peng, B., Su, M., Zhang, H. J., Hoffmann, E., Rivard, C., Green, I., Howard, T., Pollard, H., Read, J., Alimzhanov, M., Bebernitz, G., Bell, K., Ye, M., Huszar, D., and Zinda, M. (2011) Discovery of 5-chloro-N2-[(1S)-1-(5- fluoropyrimidin-2-yl)ethyl]-N4-(5-methyl-1H-pyrazol -3-yl)py-rimidine- 2,4-diamine (AZD1480) as a novel inhibitor of the Jak/Stat pathway. J. Med. Chem. 54, 262-276
100. Changelian, P. S., Flanagan, M. E., Ball, D. J., Kent, C. R., Magnuson, K. S., Martin, W. H., Rizzuti, B. J., Sawyer, P. S., Perry, B. D., Brissette, W. H., McCurdy, S. P., Kudlacz, E. M., Conklyn, M. J., Elliott, E. A., Koslov, E. R., Fisher, M. B., Strelevitz, T. J., Yoon, K., Whipple, D. A., Sun, J., Munchhof, M. J., Doty, J. L., Casavant, J. M., Blumenkopf, T. A., Hines, M., Brown, M. F., Lillie, B. M., Subramanyam, C., Shang-Poa, C., Milici, A. J., Beckius, G. E., Moyer, J. D., Su, C., Woodworth, T. G., Gaweco, A. S., Beals, C. R., Littman, B. H., Fisher, D. A., Smith, J. F., Zagouras, P., Magna, H. A., Saltarelli, M. J., Johnson, K. S., Nelms, L. F., Des Etages, S. G., Hayes, L. S., Kawabata, T. T., Finco-Kent, D., Baker, D. L., Larson, M., Si, M. S., Paniagua, R., Higgins, J., Holm, B., Reitz, B., Zhou, Y. J., Morris, R. E., O'Shea, J. J., and Borie, D. C. (2003) Prevention of organ allograft rejection by a specific Janus kinase 3 inhibitor. Science 302, 875-878
101. Wernig, G., Kharas, M. G., Okabe, R., Moore, S. A., Leeman, D. S., Cullen, D. E., Gozo, M., McDowell, E. P., Levine, R. L., Doukas, J., Mak, C. C., Noronha, G., Martin, M., Ko, Y. D., Lee, B. H., Soll, R. M., Tefferi, A., Hood, J. D., and Gilliland, D. G. (2008) Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera. Cancer Cell 13, 311-320
102. Deshpande, A., Reddy, M. M., Schade, G. O., Ray, A., Chowdary, T. K., Griffin, J. D., and Sattler, M. (2011) Kinase domain mutations confer resistance to novel inhibitors targeting JAK2V617F in myeloproliferative neoplasms. Leukemia doi:10.1038/leu.2011.255
103. Manshouri, T., Quintás-Cardama, A., Nussenzveig, R. H., Gaikwad, A., Estrov, Z., Prchal, J., Cortes, J. E., Kantarjian, H. M., and Verstovsek, S. (2008) The JAK kinase inhibitor CP-690,550 suppresses the growth of human polycythemia vera cells carrying the JAK2V617F mutation. Cancer Sci. 99, 1265-1273
104. Boschelli, D. H., Ye, F., Wang, Y. D., Dutia, M., Johnson, S. L., Wu, B., Miller, K., Powell, D. W., Yaczko, D., Young, M., Tischler, M., Arndt, K., Discafani, C., Etienne, C., Gibbons, J., Grod, J., Lucas, J., Weber, J. M., and Boschelli, F. (2001) Optimization of 4-phenylamino-3-quinolinecarbonitriles as potent inhibitors of Src kinase activity. J. Med. Chem. 44, 3965-3977
105. Golas, J. M., Arndt, K., Etienne, C., Lucas, J., Nardin, D., Gibbons, J., Frost, P., Ye, F., Boschelli, D. H., and Boschelli, F. (2003) SKI-606, a 4-anilino-3-quinolinecarbonitrile dual inhibitor of Src and Abl kinases, is a potent antiproliferative agent against chronic myelogenous leukemia cells in culture and causes regression of K562 xenografts in nude mice. Cancer Res. 63, 375-381
106. Puttini, M., Coluccia, A. M., Boschelli, F., Cleris, L., Marchesi, E., Donella- Deana, A., Ahmed, S., Redaelli, S., Piazza, R., Magistroni, V., Andreoni, F., Scapozza, L., Formelli, F., and Gambacorti-Passerini, C. (2006) In vitro and in vivo activity of SKI-606, a novel Src-Abl inhibitor, against imatinib-resistant Bcr-Abl+ neoplastic cells. Cancer Res. 66, 11314-11322
107. Advani, R. H., Sharman, J. P., Smith, S. M., Boyd, T. E., Grant, B. W., Kolibaba, K. S., Furman, R. R., Buggy, J. J., Loury, D. J., Hedrick, E., Izumi, R., Hamdy, A. M., and Fowler, N. H. (2011) The Btk inhibitor Pci-32765 Is highly active and well tolerated in patients (Pts) with relapsed/refractory B cell malignancies: final results from a phase I study. Ann. Oncol. 22, 135-135
108. Burger, J. A., O'Brien, S., Fowler, N., Advani, R., Sharman, J. P., Furman, R. R., Izumi, R., Buggy, J., Loury, D., Hamdy, A., Byrd, J. C., and Blum, K. A. (2010) The Bruton's tyrosine kinase inhibitor, PCI-32765, is well tolerated and demonstrates promising clinical activity in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL): An update on ongoing phase 1 studies. Blood 116, 32-32
109. Fowler, N., Sharman, J. P., Smith, S. M., Boyd, T., Grant, B., Kolibaba, K. S., Furman, R. R., Buggy, J., Loury, D., Hamdy, A., and Advani, R. (2010) The Btk inhibitor, PCI-32765, induces durable responses with minimal toxicity in patients with relapsed/refractory B-cell malignancies: results from a phase I study. Blood 116, 425-425
110. O'Brien, S., Burger, J.A., Coutre, S. E., Sharman, J. P., Furman, R. R., Flinn, I. W., Grant, B., Richards, D., Heerema, N., Johnson, A. J., Izumi, R., Hamdy, A., Blum, K. A., and Byrd, J. C. (2011) The Btk inhibitor Pci-32765 is highly active and tolerable in patients with poor-risk Cll: interim results from a phase Ib/Ii study. Ann. Oncol. 22, 124-124
111. Scuto, A., Krejci, P., Popplewell, L., Wu, J., Wang, Y., Kujawski, M., Kowolik, C., Xin, H., Chen, L., Wang, Y., Kretzner, L., Yu, H., Wilcox, W. R., Yen, Y., Forman, S., and Jove, R. (2011) The novel JAK inhibitor AZD1480 blocks STAT3 and FGFR3 signaling, resulting in suppression of human myeloma cell growth and survival. Leukemia 25, 538-550
112. Hedvat, M., Huszar, D., Herrmann, A., Gozgit, J. M., Schroeder, A., Sheehy, A., Buettner, R., Proia, D., Kowolik, C. M., Xin, H., Armstrong, B., Bebernitz, G., Weng, S., Wang, L., Ye, M., McEachern, K., Chen, H., Morosini, D., Bell, K., Alimzhanov, M., Ioannidis, S., McCoon, P., Cao, Z. A., Yu, H.,
113. Luo, Y., Shoemaker, A. R., Liu, X., Woods, K. W., Thomas, S. A., de Jong, R., Han, E. K., Li, T., Stoll, V. S., Powlas, J. A., Oleksijew, A., Mitten, M. J., Shi, Y., Guan, R., McGonigal, T. P., Klinghofer, V., Johnson, E. F., Leverson, J. D., Bouska, J. J., Mamo, M., Smith, R. A., Gramling-Evans, E. E., Zinker, B. A., Mika, A. K., Nguyen, P. T., Oltersdorf, T., Rosenberg, S. H., Li, Q., and Giranda, V. L. (2005) Potent and selective inhibitors of Akt kinases slow the progress of tumors in vivo. Mol. Cancer Ther. 4, 977-986
114. Rhodes, N., Heerding, D. A., Duckett, D. R., Eberwein, D. J., Knick, V. B., Lansing, T. J., McConnell, R. T., Gilmer, T. M., Zhang, S. Y., Robell, K., Kahana, J. A., Geske, R. S., Kleymenova, E. V., Choudhry, A. E., Lai, Z., Leber, J. D., Minthorn, E. A., Strum, S. L., Wood, E. R., Huang, P. S., Copeland, R. A., and Kumar, R. (2008) Characterization of an Akt kinase inhibitor with potent pharmacodynamic and antitumor activity. Cancer Res. 68, 2366-2374
115. Bennett, B. L., Sasaki, D. T., Murray, B. W., O'Leary, E. C., Sakata, S. T., Xu, W., Leisten, J. C., Motiwala, A., Pierce, S., Satoh, Y., Bhagwat, S. S., Manning, A. M., and Anderson, D. W. (2001) SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proc. Natl. Acad. Sci. U.S.A. 98, 13681-13686
116. Du, L., Lyle, C. S., Obey, T. B., Gaarde, W. A., Muir, J. A., Bennett, B. L., and Chambers, T. C. (2004) Inhibition of cell proliferation and cell cycle progression by specific inhibition of basal JNK activity: evidence that mitotic Bcl-2 phosphorylation is JNK-independent. J. Biol. Chem. 279, 11957-11966
117. Pargellis, C., Tong, L., Churchill, L., Cirillo, P. F., Gilmore, T., Graham, A. G., Grob, P. M., Hickey, E. R., Moss, N., Pav, S., and Regan, J. (2002) Inhibition of p38 MAP kinase by utilizing a novel allosteric binding site. Nat. Struct. Biol. 9, 268-272
118. Frantz, B., Klatt, T., Pang, M., Parsons, J., Rolando, A., Williams, H., Tocci, M. J., O'Keefe, S. J., and O'Neill, E. A. (1998) The activation state of p38 mitogen-activated protein kinase determines the efficiency of ATP competition for pyridinylimidazole inhibitor binding. Biochemistry 37, 13846-13853
119. Hunt, A. E., Lali, F. V., Lord, J. D., Nelson, B. H., Miyazaki, T., Tracey, K. J., and Foxwell, B. M. (1999) Role of interleukin (IL)-2 receptor beta-chain subdomains and Shc in p38 mitogen-activated protein (MAP) kinase and p54 MAP kinase (stress-activated protein Kinase/c-Jun N-terminal kinase) activation. IL-2-driven proliferation is independent of p38 and p54 MAP kinase activation. J. Biol. Chem. 274, 7591-7597
120. Fitzgerald, C. E., Patel, S. B., Becker, J. W., Cameron, P. M., Zaller, D., Pikounis, V. B., O'Keefe, S. J., and Scapin, G. (2003) Structural basis for p38alpha MAP kinase quinazolinone and pyridol-pyrimidine inhibitor specificity. Nat. Struct. Biol. 10, 764-769
121. Hideshima, T., Akiyama, M., Hayashi, T., Richardson, P., Schlossman, R., Chauhan, D., and Anderson, K. C. (2003) Targeting p38 MAPK inhibits multiple myeloma cell growth in the bone marrow milieu. Blood 101, 703-705
122. Druker, B. J., Tamura, S., Buchdunger, E., Ohno, S., Segal, G. M., Fanning, S., Zimmermann, J., and Lydon, N. B. (1996) Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat. Med. 2, 561-566
123. Deininger, M. W., Goldman, J. M., Lydon, N., and Melo, J. V. (1997) The tyrosine kinase inhibitor CGP57148B selectively inhibits the growth of BCR-ABL-positive cells. Blood 90, 3691-3698
124. Dar, A. C., Lopez, M. S., and Shokat, K. M. (2008) Small molecule recognition of c-Src via the Imatinib-binding conformation. Chem. Biol. 15, 1015-1022
125. Carroll, M., Ohno-Jones, S., Tamura, S., Buchdunger, E., Zimmermann, J., Lydon, N. B., Gilliland, D. G., and Druker, B. J. (1997) CGP 57148, a tyrosine kinase inhibitor, inhibits the growth of cells expressing BCRABL, TEL-ABL, and TEL-PDGFR fusion proteins. Blood 90, 4947-4952
126. Buchdunger, E., Zimmermann, J., Mett, H., Meyer, T., Müller, M., Druker, B. J., and Lydon, N. B. (1996) Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative. Cancer Res. 56, 100-104
127. O'Hare, T., Walters, D. K., Stoffregen, E. P., Jia, T., Manley, P. W., Mestan, J., Cowan-Jacob, S. W., Lee, F. Y., Heinrich, M. C., Deininger, M. W., and Druker, B. J. (2005) In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res. 65, 4500-4505
128. Weisberg, E., Manley, P. W., Breitenstein, W., Brüggen, J., Cowan-Jacob, S. W., Ray, A., Huntly, B., Fabbro, D., Fendrich, G., Hall-Meyers, E., Kung, A. L., Mestan, J., Daley, G. Q., Callahan, L., Catley, L., Cavazza, C., Azam, M., Neuberg, D., Wright, R. D., Gilliland, D. G., and Griffin, J. D. (2005) Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl. Cancer Cell 7, 129-141
129. Sabbatini, P., Korenchuk, S., Rowand, J. L., Groy, A., Liu, Q., Leperi, D., Atkins, C., Dumble, M., Yang, J., Anderson, K., Kruger, R. G., Gontarek, R. R., Maksimchuk, K. R., Suravajjala, S., Lapierre, R. R., Shotwell, J. B., Wilson, J. W., Chamberlain, S. D., Rabindran, S. K., and Kumar, R. (2009) GSK1838705A inhibits the insulin-like growth factor-1 receptor and anaplastic lymphoma kinase and shows antitumor activity in experimental models of human cancers. Mol. Cancer Ther. 8, 2811-2820
130. Jin, N., Jiang, T., Rosen, D. M., Nelkin, B. D., and Ball, D. W. (2011) Synergistic action of a RAF inhibitor and a dual PI3K/mTOR inhibitor in thyroid cancer. Clin. Cancer Res. 17, 6482-6489
131. Hoeflich, K. P., Herter, S., Tien, J., Wong, L., Berry, L., Chan, J., O'Brien, C., Modrusan, Z., Seshagiri, S., Lackner, M., Stern, H., Choo, E., Murray, L., Friedman, L. S., and Belvin, M. (2009) Antitumor efficacy of the novel RAF inhibitor GDC-0879 is predicted by BRAFV600E mutational status and sustained extracellular signal-regulated kinase/mitogen-activated protein kinase pathway suppression. Cancer Res. 69, 3042-3051
132. Ohno, H., Kubo, K., Murooka, H., Kobayashi, Y., Nishitoba, T., Shibuya, M., Yoneda, T., and Isoe, T. (2006) A c-fms tyrosine kinase inhibitor, Ki20227, suppresses osteoclast differentiation and osteolytic bone destruction in a bone metastasis model. Mol. Cancer Ther. 5, 2634-2643
133. Moyer, J. D., Barbacci, E. G., Iwata, K. K., Arnold, L., Boman, B., Cunningham, A., DiOrio, C., Doty, J., Morin, M. J., Moyer, M. P., Neveu, M., Pollack, V. A., Pustilnik, L. R., Reynolds, M. M., Sloan, D., Theleman, A., and Miller, P. (1997) Induction of apoptosis and cell cycle arrest by CP-358,774, an inhibitor of epidermal growth factor receptor tyrosine kinase. Cancer Res. 57, 4838-4848
134. Wakeling, A. E., Guy, S. P., Woodburn, J. R., Ashton, S. E., Curry, B. J., Barker, A. J., and Gibson, K. H. (2002) ZD1839 (Iressa): an orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy. Cancer Res. 62, 5749-5754
135. Rabindran, S. K., Discafani, C. M., Rosfjord, E. C., Baxter, M., Floyd, M. B., Golas, J., Hallett, W. A., Johnson, B. D., Nilakantan, R., Overbeek, E., Reich, M. F., Shen, R., Shi, X., Tsou, H. R., Wang, Y. F., and Wissner, A. (2004) Antitumor activity of HKI-272, an orally active, irreversible inhibitor of the HER-2 tyrosine kinase. Cancer Res. 64, 3958-3965
136. Huang, H. L., Chen, Y. C., Huang, Y. C., Yang, K. C., Pan, H. Y., Shih, S. P., and Chen, Y. J. (2011) Lapatinib induces autophagy, apoptosis and megakaryocytic differentiation in chronic myelogenous leukemia k562 cells. PLoS One 6, e29014
137. Wood, E. R., Truesdale, A. T., McDonald, O. B., Yuan, D., Hassell, A., Dickerson, S. H., Ellis, B., Pennisi, C., Horne, E., Lackey, K., Alligood, K. J., Rusnak, D. W., Gilmer, T. M., and Shewchuk, L. (2004) A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib): relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells. Cancer Res. 64, 6652-6659
138. Albert, D. H., Tapang, P., Magoc, T. J., Pease, L. J., Reuter, D. R., Wei, R. Q., Li, J., Guo, J., Bousquet, P. F., Ghoreishi-Haack, N. S., Wang, B., Bukofzer, G. T., Wang, Y. C., Stavropoulos, J. A., Hartandi, K., Niquette, A. L., Soni, N., Johnson, E. F., McCall, J. O., Bouska, J. J., Luo, Y., Donawho, C. K., Dai, Y., Marcotte, P. A., Glaser, K. B., Michaelides, M. R., and Davidsen, S. K. (2006) Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor. Mol. Cancer Ther. 5, 995-1006
139. Kelly, L. M., Yu, J. C., Boulton, C. L., Apatira, M., Li, J., Sullivan, C. M., Williams, I., Amaral, S. M., Curley, D. P., Duclos, N., Neuberg, D., Scarborough, R. M., Pandey, A., Hollenbach, S., Abe, K., Lokker, N. A., Gilliland, D. G., and Giese, N. A. (2002) CT53518, a novel selective FLT3 antagonist for the treatment of acute myelogenous leukemia (AML). Cancer Cell 1, 421-432
140. Qian, F., Engst, S., Yamaguchi, K., Yu, P., Won, K. A., Mock, L., Lou, T., Tan, J., Li, C., Tam, D., Lougheed, J., Yakes, F. M., Bentzien, F., Xu, W., Zaks, T., Wooster, R., Greshock, J., and Joly, A. H. (2009) Inhibition of tumor cell growth, invasion, and metastasis by EXEL-2880 (XL880, GSK1363089), a novel inhibitor of HGF and VEGF receptor tyrosine kinases. Cancer Res. 69, 8009-8016
141. Buchanan, S. G., Hendle, J., Lee, P. S., Smith, C. R., Bounaud, P. Y., Jessen, K. A., Tang, C. M., Huser, N. H., Felce, J. D., Froning, K J., Peterman, M. C., Aubol, B. E., Gessert, S. F., Sauder, J. M., Schwinn, K. D., Russell, M., Rooney, I. A., Adams, J., Leon, B. C., Do, T. H., Blaney, J. M., Sprengeler, P. A., Thompson, D. A., Smyth, L., Pelletier, L. A., Atwell, S., Holme, K., Wasserman, S. R., Emtage, S., Burley, S. K., and Reich, S. H. (2009) SGX523 is an exquisitely selective, ATP-competitive inhibitor of the MET receptor tyrosine kinase with antitumor activity in vivo. Mol. Cancer Ther. 8, 3181-3190
142. Wood, J. M., Bold, G., Buchdunger, E., Cozens, R., Ferrari, S., Frei, J., Hofmann, F., Mestan, J., Mett, H., O'Reilly, T., Persohn, E., Rosel, J., Schnell, C., Stover, D., Theuer, A., Towbin, H., Wenger, F., Woods- Cook, K., Menrad, A., Siemeister, G., Schirner, M., Thierauch, K. H., Schneider, M. R., Drevs, J., Martiny-Baron, G., and Totzke, F. (2000) PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration. Cancer Res. 60, 2178-2189