The kinase ALK stimulates the kinase ERK5 to promote the expression of the oncogene MYCN in neuroblastoma

Science Signaling

Volumn 7, Issue 349, 2014, Pages

  Umapathy, Ganesh ^a   Wakil, Abeer El ^b,f   Witek, Barbara ^b   Chesler, Louis ^c   Danielson, Laura ^c   Deng, Xianming ^d,e   Gray, Nathanael S ^e   Johansson, Mikael ^b   Kvarnbrink, Samuel ^b   Ruuth, Kristina ^b   Schönherr, Christina ^b   Palmer, Ruth H ^a,b   Hallberg, Bengt ^a  

^a UNIVERSITY OF GOTHENBURG   (Sweden)

^b UMEÅ UNIVERSITY   (Sweden)

^c INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^d XIAMEN UNIVERSITY   (China)

^e HARVARD MEDICAL SCHOOL   (United States)

^f Alexandria University   (Egypt)

Author keywords

[No Author keywords available]

Indexed keywords

1,4 DIAMINO 1,4 BIS(2 AMINOPHENYLTHIO) 2,3 DICYANOBUTADIENE; ANAPLASTIC LYMPHOMA KINASE; ANTINEOPLASTIC AGENT; AZD 8055; CRIZOTINIB; DACTOLISIB; MESSENGER RNA; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 7; MITOGEN ACTIVATED PROTEIN KINASE KINASE KINASE 3; MYC N PROTEIN; ONCOPROTEIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PROTEIN SERINE THREONINE KINASE INHIBITOR; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; XMD 8 92; GREEN FLUORESCENT PROTEIN; MYCN PROTEIN, HUMAN; NUCLEAR PROTEIN; PRIMER DNA; PROTEIN TYROSINE KINASE;

ANIMAL EXPERIMENT; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; ARTICLE; CANCER COMBINATION CHEMOTHERAPY; CELL PROLIFERATION; DRUG EFFICACY; DRUG POTENTIATION; ENZYME ACTIVITY; ENZYME PHOSPHORYLATION; HUMAN; IMMUNOFLUORESCENCE; IMMUNOHISTOCHEMISTRY; IMMUNOPRECIPITATION; IN VITRO STUDY; MALE; MOUSE; NEUROBLASTOMA; NONHUMAN; PROTEIN EXPRESSION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RNA INTERFERENCE; TUMOR XENOGRAFT; ANIMAL; FLUORESCENT ANTIBODY TECHNIQUE; GENE EXPRESSION REGULATION; GENETICS; IMAGE PROCESSING; IMMUNOBLOTTING; METABOLISM; NUCLEAR MAGNETIC RESONANCE IMAGING; PATHOPHYSIOLOGY; PC12 CELL LINE; PHYSIOLOGY; RAT; REAL TIME POLYMERASE CHAIN REACTION; TUMOR CELL LINE;

ANIMALS; CELL LINE, TUMOR; DNA PRIMERS; FLUORESCENT ANTIBODY TECHNIQUE; GENE EXPRESSION REGULATION, NEOPLASTIC; GREEN FLUORESCENT PROTEINS; HUMANS; IMAGE PROCESSING, COMPUTER-ASSISTED; IMMUNOBLOTTING; IMMUNOHISTOCHEMISTRY; IMMUNOPRECIPITATION; MAGNETIC RESONANCE IMAGING; MITOGEN-ACTIVATED PROTEIN KINASE 7; NEUROBLASTOMA; NUCLEAR PROTEINS; ONCOGENE PROTEINS; PC12 CELLS; RATS; REAL-TIME POLYMERASE CHAIN REACTION; RECEPTOR PROTEIN-TYROSINE KINASES; RNA INTERFERENCE;

EID: 84908565521     PISSN: 19450877     EISSN: 19379145     Source Type: Journal    
DOI: 10.1126/scisignal.2005470     Document Type: Article

References (63)

1. S. W. Morris, M. N. Kirstein, M. B. Valentine, K. G. Dittmer, D. N. Shapiro, D. L. Saltman, A. T. Look, Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non- Hodgkin's lymphoma. Science 263, 1281-1284 (1994).
2. M. Shiota, J. Fujimoto, T. Semba, H. Satoh, T. Yamamoto, S. Mori, Hyperphosphorylation of a novel 80 kDa protein-tyrosine kinase similar to Ltk in a human Ki-1 lymphoma cell line, AMS3. Oncogene 9, 1567-1574 (1994).
3. B. Hallberg, R. H. Palmer, Mechanistic insight into ALK receptor tyrosine kinase in human cancer biology. Nat. Rev. Cancer 13, 685-700 (2013).
4. D. R. Camidge, Y. J. Bang, E. L. Kwak, A. J. Iafrate, M. Varella-Garcia, S. B. Fox, G. J. Riely, B. Solomon, S. H. Ou, D. W. Kim, R. Salgia, P. Fidias, J. A. Engelman, L. Gandhi, P. A. Jänne, D. B. Costa, G. I. Shapiro, P. Lorusso, K. Ruffner, P. Stephenson, Y. Tang, K. Wilner, J. W. Clark, A. T. Shaw, Activity and safety of crizotinib in patients with ALKpositive non-small-cell lung cancer: Updated results from a phase 1 study. Lancet Oncol. 13, 1011-1019 (2012).
5. B. Hallberg, R. H. Palmer, ALK and NSCLC: Targeted therapy with ALK inhibitors. F1000 Med. Rep. 3, 21 (2011).
6. A. T. Shaw, D. W. Kim, K. Nakagawa, T. Seto, L. Crinó, M. J. Ahn, T. De Pas, B. Besse, B. J. Solomon, F. Blackhall, Y. L. Wu, M. Thomas, K. J. O'Byrne, D. Moro-Sibilot, D. R. Camidge, T. Mok, V. Hirsh, G. J. Riely, S. Iyer, V. Tassell, A. Polli, K. D. Wilner, P. A. Jänne, Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N. Engl. J. Med. 368, 2385-2394 (2013).
7. H. Carén, F. Abel, P. Kogner, T. Martinsson, High incidence of DNA mutations and gene amplifications of the ALK gene in advanced sporadic neuroblastoma tumours. Biochem. J. 416, 153-159 (2008).
8. Y. Chen, J. Takita, Y. L. Choi, M. Kato, M. Ohira, M. Sanada, L. Wang, M. Soda, A. Kikuchi, T. Igarashi, A. Nakagawara, Y. Hayashi, H. Mano, S. Ogawa, Oncogenic mutations of ALK kinase in neuroblastoma. Nature 455, 971-974 (2008).
9. R. E. George, T. Sanda, M. Hanna, S. Fröhling, W. Luther II, J. Zhang, Y. Ahn, W. Zhou, W. B. London, P. McGrady, L. Xue, S. Zozulya, V. E. Gregor, T. R. Webb, N. S. Gray, D. G. Gilliland, L. Diller, H. Greulich, S. W. Morris, M. Meyerson, A. T. Look, Activating mutations in ALK provide a therapeutic target in neuroblastoma. Nature 455, 975-978 (2008).
10. I. Janoueix-Lerosey, D. Lequin, L. Brugières, A. Ribeiro, L. de Pontual, V. Combaret, V. Raynal, A. Puisieux, G. Schleiermacher, G. Pierron, D. Valteau-Couanet, T. Frebourg, J. Michon, S. Lyonnet, J. Amiel, O. Delattre, Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma. Nature 455, 967-970 (2008).
11. Y. P. Mossé, M. Laudenslager, L. Longo, K. A. Cole, A.Wood, E. F. Attiyeh, M. J. Laquaglia, R. Sennett, J. E. Lynch, P. Perri, G. Laureys, F. Speleman, C. Kim, C. Hou, H. Hakonarson, A. Torkamani, N. J. Schork, G. M. Brodeur, G. P. Tonini, E. Rappaport, M. Devoto, J. M. Maris, Identification of ALK as a major familial neuroblastoma predisposition gene. Nature 455, 930-935 (2008).
12. J. M. Maris, M. D. Hogarty, R. Bagatell, S. L. Cohn, Neuroblastoma. Lancet 369, 2106-2120 (2007).
13. N. K. V. Cheung, M. A. Dyer, Neuroblastoma: Developmental biology, cancer genomics and immunotherapy. Nat. Rev. Cancer 13, 397-411 (2013).
14. S. De Brouwer, K. De Preter, C. Kumps, P. Zabrocki, M. Porcu, E. M.Westerhout, A. Lakeman, J. Vandesompele, J. Hoebeeck, T. Van Maerken, A. De Paepe, G. Laureys, J. H. Schulte, A. Schramm, C. Van Den Broecke, J. Vermeulen, N. Van Roy, K. Beiske, M. Renard, R. Noguera, O. Delattre, I. Janoueix-Lerosey, P. Kogner, T. Martinsson, A. Nakagawara, M. Ohira, H. Caron, A. Eggert, J. Cools, R. Versteeg, F. Speleman, Meta-analysis of neuroblastomas reveals a skewed ALK mutation spectrum in tumors with MYCN amplification. Clin. Cancer Res. 16, 4353-4362 (2010).
15. E. Michels, J. Vandesompele, K. De Preter, J. Hoebeeck, J. Vermeulen, A. Schramm, J. J. Molenaar, B.Menten, B.Marques, R. L. Stallings, V. Combaret, C. Devalck, A. De Paepe, R. Versteeg, A. Eggert, G. Laureys, N. Van Roy, F. Speleman, ArrayCGH-based classification of neuroblastoma into genomic subgroups. Genes Chromosomes Cancer 46, 1098-1108 (2007).
16. J. Vandesompele,M. Baudis, K. De Preter, N. Van Roy, P. Ambros, N. Bown, C. Brinkschmidt, H. Christiansen, V. Combaret, M. Lastowska, J. Nicholson, A. O'Meara, D. Plantaz, R. Stallings, B. Brichard, C. Van den Broecke, S. De Bie, A. De Paepe, G. Laureys, F. Speleman, Unequivocal delineation of clinicogenetic subgroups and development of a new model for improved outcome prediction in neuroblastoma. J. Clin. Oncol. 23, 2280-2299 (2005).
17. S. Goto, S. Umehara, R. B. Gerbing, D. O. Stram, G. M. Brodeur, R. C. Seeger, J. N. Lukens, K. K. Matthay, H. Shimada, Histopathology (International Neuroblastoma Pathology Classification) and MYCN status in patients with peripheral neuroblastic tumors: A report from the Children's Cancer Group. Cancer 92, 2699-2708 (2001).
18. Y. P. Mossé,M. S. Lim, S.D. Voss, K.Wilner, K. Ruffner, J. Laliberte, D.Rolland, F. M.Balis, J. M. Maris, B. J. Weigel, A. M. Ingle, C. Ahern, P. C. Adamson, S. M. Blaney, Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic largecell lymphoma: A Children's Oncology Group phase 1 consortium study. Lancet Oncol. 14, 472-480 (2013).
19. T. Berry, W. Luther, N. Bhatnagar, Y. Jamin, E. Poon, T. Sanda, D. Pei, B. Sharma, W. R. Vetharoy, A. Hallsworth, Z. Ahmad, K. Barker, L. Moreau, H. Webber, W. Wang, Q. Liu, A. Perez-Atayde, S. Rodig, N. K. Cheung, F. Raynaud, B. Hallberg, S. P. Robinson, N. S. Gray, A. D. Pearson, S. A. Eccles, L. Chesler, R. E. George, The ALKF1174L mutation potentiates the oncogenic activity of MYCN in neuroblastoma. Cancer Cell 22, 117-130 (2012).
20. K. Sattu, F. Hochgräfe, J. Wu, G. Umapathy, C. Schönherr, K. Ruuth, D. Chand, B.Witek, J. Fuchs, P. K. Li, F. Hugosson, R. J. Daly, R. H. Palmer, B. Hallberg, Phosphoproteomic analysis of anaplastic lymphoma kinase (ALK) downstream signaling pathways identifies signal transducer and activator of transcription 3 as a functional target of activated ALK in neuroblastoma cells. FEBS J. 280, 5269-5282 (2013).
21. J. D. Lee, R. J. Ulevitch, J. H. Han, Primary structure of BMK1: A new mammalian map kinase. Biochem. Biophys. Res. Commun. 213, 715-724 (1995).
22. G. C. Zhou, Z. Q. Bao, J. E. Dixon, Components of a new human protein kinase signal transduction pathway. J. Biol. Chem. 270, 12665-12669 (1995).
23. G. N. Nithianandarajah-Jones, B. Wilm, C. E. P. Goldring, J. Müller, M. J. Cross, ERK5: Structure, regulation and function. Cell. Signal. 24, 2187-2196 (2012).
24. B. A. Drew, M. E. Burow, B. S. Beckman, MEK5/ERK5 pathway: The first fifteen years. Biochim. Biophys. Acta 1825, 37-48 (2012).
25. M. Buschbeck, A. Ullrich, The unique C-terminal tail of the mitogen-activated protein kinase ERK5 regulates its activation and nuclear shuttling. J. Biol. Chem. 280, 2659-2667 (2005).
26. S. Nishimoto, E. Nishida, MAPK signalling: ERK5 versus ERK1/2. EMBO Rep. 7, 782-786 (2006).
27. H. G. Kasler, J. Victoria, O. Duramad, A. Winoto, ERK5 is a novel type of mitogenactivated protein kinase containing a transcriptional activation domain. Mol. Cell. Biol. 20, 8382-8389 (2000).
28. T. Tanoue, E. Nishida, Docking interactions in the mitogen-activated protein kinase cascades. Pharmacol. Ther. 93, 193-202 (2002).
29. C. Yan, H. L. Luo, J. D. Lee, J. I. Abe, B. C. Berk, Molecular cloning of mouse ERK5/BMK1 splice variants and characterization of ERK5 functional domains. J. Biol. Chem. 276, 10870-10878 (2001).
30. T. H. Chao, M. Hayashi, R. I. Tapping, Y. Kato, J. D. Lee, MEKK3 directly regulates MEK5 activity as part of the big mitogen-activated protein kinase 1 (BMK1) signaling pathway. J. Biol. Chem. 274, 36035-36038 (1999).
31. W. Sun, X. Wei, K. Kesavan, T. P. Garrington, R. Fan, J.Mei, S. M. Anderson, E.W. Gelfand, G. L. Johnson, MEK kinase 2 and the adaptor protein Lad regulate extracellular signalregulated kinase 5 activation by epidermal growth factor via Src. Mol. Cell. Biol. 23, 2298-2308 (2003).
32. L. Yan, J. Carr, P. R. Ashby, V. Murry-Tait, C. Thompson, J. S. Arthur, Knockout of ERK5 causes multiple defects in placental and embryonic development. BMC Dev. Biol. 3, 11 (2003).
33. M. Hayashi, S. W. Kim, K. Imanaka-Yoshida, T. Yoshida, E. D. Abel, B. Eliceiri, Y. Yang, R. J. Ulevitch, J. D. Lee, Targeted deletion of BMK1/ERK5 in adult mice perturbs vascular integrity and leads to endothelial failure. J. Clin. Invest. 113, 1138-1148 (2004).
34. Q. Yang, X. Deng, B. Lu, M. Cameron, C. Fearns, M. P. Patricelli, J. R. Yates III, N. S. Gray, J. D. Lee, Pharmacological inhibition of BMK1 suppresses tumor growth through promyelocytic leukemia protein. Cancer Cell 18, 258-267 (2010).
35. C. Schönherr, K. Ruuth, S. Kamaraj, C. L. Wang, H. L. Yang, V. Combaret, A. Djos, T. Martinsson, J. G. Christensen, R. H. Palmer, B. Hallberg, Anaplastic lymphoma kinase (ALK) regulates initiation of transcription of MYCN in neuroblastoma cells. Oncogene 31, 5193-5200 (2012).
36. A. Cazes, C. Louis-Brennetot, P. Mazot, F. Dingli, B. Lombard, V. Boeva, R. Daveau, J. Cappo, V. Combaret, G. Schleiermacher, S. Jouannet, S. Ferrand, G. Pierron, E. Barillot, D. Loew, M. Vigny, O. Delattre, I. Janoueix-Lerosey, Characterization of rearrangements involving the ALK gene reveals a novel truncated form associated with tumor aggressiveness in neuroblastoma. Cancer Res. 73, 195-204 (2013).
37. G. Schleiermacher, I. Janoueix-Lerosey, V. Combaret, J. Derré, J. Couturier, A. Aurias, O. Delattre, Combined 24-color karyotyping and comparative genomic hybridization analysis indicates predominant rearrangements of early replicating chromosome regions in neuroblastoma. Cancer Genet. Cytogenet. 141, 32-42 (2003).
38. N. E. Kohl, C. E. Gee, F. W. Alt, Activated expression of the N-myc gene in human neuroblastomas and related tumors. Science 226, 1335-1337 (1984).
39. L. Chesler, C. Schlieve, D. D. Goldenberg, A. Kenney, G. Kim, A. McMillan, K. K. Matthay, D. Rowitch, W. A. Weiss, Inhibition of phosphatidylinositol 3-kinase destabilizes Mycn protein and blocks malignant progression in neuroblastoma. Cancer Res. 66, 8139-8146 (2006).
40. W. C. Gustafson, W. A. Weiss, Myc proteins as therapeutic targets. Oncogene 29, 1249-1259 (2010).
41. J. G. Christensen, H. Y. Zou, M. E. Arango, Q. Li, J. H. Lee, S. R. McDonnell, S. Yamazaki, G. R. Alton, B. Mroczkowski, G. Los, Cytoreductive antitumor activity of PF-2341066, a novel inhibitor of anaplastic lymphoma kinase and c-Met, in experimental models of anaplastic large-cell lymphoma. Mol. Cancer Ther. 6, 3314-3322 (2007).
42. X. Deng, J. Wang, J. Zhang, T. Sim, N. D. Kim, T. Sasaki, W. Luther II, R. E. George, P. A. Jänne, N. S. Gray, Discovery of 3,5-diamino-1,2,4-triazole ureas as potent anaplastic lymphoma kinase inhibitors. ACS Med. Chem. Lett. 2, 379-384 (2011).
43. S. Wennström, J. Downward, Role of phosphoinositide 3-kinase in activation of ras and mitogen-activated protein kinase by epidermal growth factor. Mol. Cell. Biol. 19, 4279-4288 (1999).
44. M. Hayashi, J. D. Lee, Role of the BMK1/ERK5 signaling pathway: Lessons from knockout mice. J. Mol. Med. 82, 800-808 (2004).
45. Y. Kato, V. V. Kravchenko, R. I. Tapping, J. Han, R. J. Ulevitch, J. D. Lee, BMK1/ERK5 regulates serum-induced early gene expression through transcription factor MEF2C. EMBO J. 16, 7054-7066 (1997).
46. D. R. Alessi, F. B. Caudwell, M. Andjelkovic, B. A. Hemmings, P. Cohen, Molecular basis for the substrate specificity of protein kinase B; comparison with MAPKAP kinase-1 and p70 S6 kinase. FEBS Lett. 399, 333-338 (1996).
47. K. Kondoh, K. Terasawa, H. Morimoto, E. Nishida, Regulation of nuclear translocation of extracellular signal-regulated kinase 5 by active nuclear import and export mechanisms. Mol. Cell. Biol. 26, 1679-1690 (2006).
48. R. Sears, F. Nuckolls, E. Haura, Y. Taya, K. Tamai, J. R. Nevins, Multiple Rasdependent phosphorylation pathways regulate Myc protein stability. Genes Dev. 14, 2501-2514 (2000).
49. T. C. Chou, P. Talalay, Quantitative analysis of dose-effect relationships: The combined effects of multiple drugs or enzyme inhibitors. Adv. Enzyme Regul. 22, 27-55 (1984).
50. G. M. Brodeur, R. C. Seeger, M. Schwab, H. E. Varmus, J. M. Bishop, Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science 224, 1121-1124 (1984).
51. W. A. Weiss, K. Aldape, G. Mohapatra, B. G. Feuerstein, J. M. Bishop, Targeted expression of MYCN causes neuroblastoma in transgenic mice. EMBO J. 16, 2985-2995 (1997).
52. S. Zhu, J. S. Lee, F. Guo, J. Shin, A. R. Perez-Atayde, J. L. Kutok, S. J. Rodig, D. S. Neuberg, D. Helman, H. Feng, R. A. Stewart, W. Wang, R. E. George, J. P. Kanki, A. T. Look, Activated ALK collaborates with MYCN in neuroblastoma pathogenesis. Cancer Cell 21, 362-373 (2012).
53. M. K. Hasan, A. Nafady, A. Takatori, S. Kishida, M. Ohira, Y. Suenaga, S. Hossain, J. Akter, A. Ogura, Y. Nakamura, K. Kadomatsu, A. Nakagawara, ALK is a MYCN target gene and regulates cell migration and invasion in neuroblastoma. Sci. Rep. 3, 3450 (2013).
54. G. Barone, J. Anderson, A. D. Pearson, K. Petrie, L. Chesler, New strategies in neuroblastoma: Therapeutic targeting of MYCN and ALK. Clin. Cancer Res. 19, 5814-5821 (2013).
55. T. J. Pugh, O. Morozova, E. F. Attiyeh, S. Asgharzadeh, J. S. Wei, D. Auclair, S. L. Carter, K. Cibulskis, M. Hanna, A. Kiezun, J. Kim, M. S. Lawrence, L. Lichenstein, A. McKenna, C. S. Pedamallu, A. H. Ramos, E. Shefler, A. Sivachenko, C. Sougnez, C. Stewart, A. Ally, I. Birol, R. Chiu, R. D. Corbett, M. Hirst, S. D. Jackman, B. Kamoh, A. H. Khodabakshi, M. Krzywinski, A. Lo, R. A. Moore, K. L. Mungall, J. Qian, A. Tam, N. Thiessen, Y. Zhao, K. A. Cole, M. Diamond, S. J. Diskin, Y. P. Mosse, A. C.Wood, L. Ji, R. Sposto, T. Badgett, W. B. London, Y. Moyer, J. M. Gastier-Foster, M. A. Smith, J. M. Guidry Auvil, D. S. Gerhard, M. D. Hogarty, S. J. Jones, E. S. Lander, S. B. Gabriel, G. Getz, R. C. Seeger, J. Khan, M. A. Marra, M. Meyerson, J. M. Maris, The genetic landscape of high-risk neuroblastoma. Nat. Genet. 45, 279-284 (2013).
56. T. Martinsson, T. Eriksson, J. Abrahamsson, H. Caren, M. Hansson, P. Kogner, S. Kamaraj, C. Schönherr, J. Weinmar, K. Ruuth, R. H. Palmer, B. Hallberg, Appearance of the novel activating F1174S ALK mutation in neuroblastoma correlates with aggressive tumour progression and unresponsiveness to therapy. Cancer Res. 71, 98-105 (2011).
57. G. Schleiermacher, N. Javanmardi, V. Bernard, Q. Leroy, J. Cappo, T. Rio Frio, G. Pierron, E. Lapouble, V. Combaret, F. Speleman, B. deWilde, A. Djos, I. Ora, F. Hedborg, C. Träger, B. M. Holmqvist, J. Abrahamsson, M. Peuchmaur, J. Michon, I. Janoueix-Lerosey, P. Kogner, O. Delattre, T. Martinsson, Emergence of new ALK mutations at relapse of neuroblastoma. J. Clin. Oncol. 32, 2727-2734 (2014).
58. Y. L. Choi, M. Soda, Y. Yamashita, T. Ueno, J. Takashima, T. Nakajima, Y. Yatabe, K. Takeuchi, T. Hamada, H. Haruta, Y. Ishikawa, H. Kimura, T. Mitsudomi, Y. Tanio, H. Mano; ALK Lung Cancer Study Group, EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. N. Engl. J. Med. 363, 1734-1739 (2010).
59. R. Katayama, A. T. Shaw, T. M. Khan, M. Mino-Kenudson, B. J. Solomon, B. Halmos, N. A. Jessop, J. C. Wain, A. T. Yeo, C. Benes, L. Drew, J. C. Saeh, K. Crosby, L. V. Sequist, A. J. Iafrate, J. A. Engelman, Mechanisms of acquired crizotinib resistance in ALKrearranged lung cancers. Sci. Transl. Med. 4, 120ra17 (2012).
60. H. L. Yang, T. Eriksson, E. Vernersson, M. Vigny, B. Hallberg, R. H. Palmer, The ligand Jelly Belly (Jeb) activates the Drosophila Alk RTK to drive PC12 cell differentiation, but is unable to activate the Mouse ALK RTK. J. Exp. Zool. B Mol. Dev. Evol. 308, 269-282 (2007).
61. C. Schönherr, H. L. Yang, M. Vigny, R. H. Palmer, B. Hallberg, Anaplastic lymphoma kinase activates the small GTPase Rap1 via the Rap1-specific GEF C3G in both neuroblastoma and PC12 cells. Oncogene 29, 2817-2830 (2010).
62. E. Kurin, A. G. Atanasov, O. Donath, E. H. Heiss, V. M. Dirsch, M. Nagy, Synergy study of the inhibitory potential of red wine polyphenols on vascular smooth muscle cell proliferation. Planta Med. 78, 772-778 (2012).
63. J. O'Brien, I. Wilson, T. Orton, F. Pognan, Investigation of the Alamar Blue (resazurin) fluorescent dye for the assessment of mammalian cell cytotoxicity. Eur. J. Biochem. 267, 5421-5426 (2000).