The constitutive activation of Jak2-V617F is mediated by a π stacking mechanism involving Phenylalanines 595 and 617

Biochemistry

Volumn 49, Issue 46, 2010, Pages 9972-9984

  Gnanasambandan, Kavitha ^a   Magis, Andrew ^b   Sayeski, Peter P ^a  

^a UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

^b UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AROMATICITIES; AUTOPHOSPHORYLATION; CHARGED RESIDUES; GENE TRANSCRIPTIONS; HUMAN DISEASE; HYDROPATHY INDEX; IN-VITRO; KINASE ACTIVATION; KINASE ACTIVITY; MOLECULAR BASIS; MOLECULAR DYNAMICS SIMULATIONS; SITE DIRECTED MUTAGENESIS; SOMATIC MUTATION; STACKING INTERACTION;

AMINO ACIDS; CHEMICAL ACTIVATION; MOLECULAR DYNAMICS; TRANSCRIPTION;

PROTEINS;

JANUS KINASE 2; PHENYLALANINE; VALINE;

AMINO ACID SUBSTITUTION; ARTICLE; AUTOPHOSPHORYLATION; ENZYME ACTIVATION; GENETIC TRANSCRIPTION; MOLECULAR DYNAMICS; MOLECULAR MODEL; PRIORITY JOURNAL; PROTEIN INTERACTION; PROTEIN STRUCTURE; SITE DIRECTED MUTAGENESIS;

ANIMALS; CERCOPITHECUS AETHIOPS; COMPUTER SIMULATION; COS CELLS; HUMANS; JANUS KINASE 2; MODELS, MOLECULAR; MUTATION, MISSENSE; PHENYLALANINE; PROTEIN CONFORMATION; TRANSFECTION;

EID: 78649289718     PISSN: 00062960     EISSN: 15204995     Source Type: Journal    
DOI: 10.1021/bi1014858     Document Type: Article

References (43)

1. Neubauer, H., Cumano, A., Muller, M., Wu, H., Huffstadt, U., and Pfeffer, K. (1998) Jak2 deficiency defines an essential developmental checkpoint in definitive hematopoiesis Cell 93, 397-409
2. Parganas, E., Wang, D., Stravopodis, D., Topham, D. J., Marine, J. C., Teglund, S., Vanin, E. F., Bodner, S., Colamonici, O. R., van Deursen, J. M., Grosveld, G., and Ihle, J. N. (1998) Jak2 is essential for signaling through a variety of cytokine receptors Cell 93, 385-395
3. Sandberg, E. M., Wallace, T. A., Godeny, M. D., VonDerLinden, D., and Sayeski, P. P. (2004) Jak2 tyrosine kinase: a true jak of all trades? Cell Biochem. Biophys. 41, 207-232
4. Witthuhn, B. A., Quelle, F. W., Silvennoinen, O., Yi, T., Tang, B., Miura, O., and Ihle, J. N. (1993) JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin Cell 74, 227-236
5. Levine, R. L. and Gilliland, D. G. (2008) Myeloproliferative disorders Blood 112, 2190-2198
6. Levine, R. L., Pardanani, A., Tefferi, A., and Gilliland, D. G. (2007) Role of JAK2 in the pathogenesis and therapy of myeloproliferative disorders Nat. Rev. Cancer 7, 673-683
7. Baxter, E. J., Scott, L. M., Campbell, P. J., East, C., Fourouclas, N., Swanton, S., Vassiliou, G. S., Bench, A. J., Boyd, E. M., Curtin, N., Scott, M. A., Erber, W. N., and Green, A. R. (2005) Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders Lancet 365, 1054-1061
8. James, C., Ugo, V., Le Couedic, J. P., Staerk, J., Delhommeau, F., Lacout, C., Garcon, L., Raslova, H., Berger, R., Bennaceur-Griscelli, A., Villeval, J. L., Constantinescu, S. N., Casadevall, N., and Vainchenker, W. (2005) A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera Nature 434, 1144-1148 (Pubitemid 40663494)
9. Kralovics, R., Passamonti, F., Buser, A. S., Teo, S. S., Tiedt, R., Passweg, J. R., Tichelli, A., Cazzola, M., and Skoda, R. C. (2005) A gain-of-function mutation of JAK2 in myeloproliferative disorders N. Engl. J. Med. 352, 1779-1790 (Pubitemid 40570926)
10. Levine, R. L., Wadleigh, M., Cools, J., Ebert, B. L., Wernig, G., Huntly, B. J., Boggon, T. J., Wlodarska, I., Clark, J. J., Moore, S., Adelsperger, J., Koo, S., Lee, J. C., Gabriel, S., Mercher, T., D'Andrea, A., Frohling, S., Dohner, K., Marynen, P., Vandenberghe, P., Mesa, R. A., Tefferi, A., Griffin, J. D., Eck, M. J., Sellers, W. R., Meyerson, M., Golub, T. R., Lee, S. J., and Gilliland, D. G. (2005) Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis Cancer Cell 7, 387-397
11. Zhao, R., Xing, S., Li, Z., Fu, X., Li, Q., Krantz, S. B., and Zhao, Z. J. (2005) Identification of an acquired JAK2 mutation in polycythemia vera J. Biol. Chem. 280, 22788-22792
12. Saharinen, P., Vihinen, M., and Silvennoinen, O. (2003) Autoinhibition of Jak2 tyrosine kinase is dependent on specific regions in its pseudokinase domain Mol. Biol. Cell 14, 1448-1459
13. Zhao, L., Ma, Y., Seemann, J., and Huang, L. J. (2010) A regulating role of the JAK2 FERM domain in hyperactivation of JAK2(V617F) Biochem. J. 426, 91-98
14. Lucet, I. S., Fantino, E., Styles, M., Bamert, R., Patel, O., Broughton, S. E., Walter, M., Burns, C. J., Treutlein, H., Wilks, A. F., and Rossjohn, J. (2006) The structural basis of Janus kinase 2 inhibition by a potent and specific pan-Janus kinase inhibitor Blood 107, 176-183
15. Lindauer, K., Loerting, T., Liedl, K. R., and Kroemer, R. T. (2001) Prediction of the structure of human Janus kinase 2 (JAK2) comprising the two carboxy-terminal domains reveals a mechanism for autoregulation Protein Eng. 14, 27-37
16. Giordanetto, F. and Kroemer, R. T. (2002) Prediction of the structure of human Janus kinase 2 (JAK2) comprising JAK homology domains 1 through 7 Protein Eng. 15, 727-737
17. McGaughey, G. B., Gagne, M., and Rappe, A. K. (1998) pi-Stacking interactions. Alive and well in proteins J. Biol. Chem. 273, 15458-15463
18. Churchill, C. D., Navarro-Whyte, L., Rutledge, L. R., and Wetmore, S. D. (2009) Effects of the biological backbone on DNA-protein stacking interactions Phys. Chem. Chem. Phys. 11, 10657-10670
19. Fiedor, J., Pilch, M., and Fiedor, L. (2009) Tuning the thermodynamics of association of transmembrane helices J. Phys. Chem. B 113, 12831-12838
20. Gazit, E. (2002) A possible role for pi-stacking in the self-assembly of amyloid fibrils FASEB J. 16, 77-83
21. Phillips, J. C., Braun, R., Wang, W., Gumbart, J., Tajkhorshid, E., Villa, E., Chipot, C., Skeel, R. D., Kale, L., and Schulten, K. (2005) Scalable molecular dynamics with NAMD J. Comput. Chem. 26, 1781-1802
22. Zhang, L. and Hermans, J. (1996) Hydrophilicity of cavities in proteins Proteins 24, 433-438
23. Brooks, B. R., Bruccoleri, R. E., Olafson, B. D., States, D. J., Swaminathan, S., and Karplus, M. J. (1983) CHARMM: a program for macromolecular energy, minimization, and dynamics calculations J. Comput. Chem. 4, 187-217
24. Ali, M. S., Sayeski, P. P., Dirksen, L. B., Hayzer, D. J., Marrero, M. B., and Bernstein, K. E. (1997) Dependence on the motif YIPP for the physical association of Jak2 kinase with the intracellular carboxyl tail of the angiotensin II AT1 receptor J. Biol. Chem. 272, 23382-23388
25. Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., and Ferrin, T. E. (2004) UCSF Chimera-a visualization system for exploratory research and analysis J. Comput. Chem. 25, 1605-1612
26. Humphrey, W., Dalke, A., and Schulten, K. (1996) VMD: visual molecular dynamics J. Mol. Graphics 14 (33-38) 27-38
27. Feng, J., Witthuhn, B. A., Matsuda, T., Kohlhuber, F., Kerr, I. M., and Ihle, J. N. (1997) Activation of Jak2 catalytic activity requires phosphorylation of Y1007 in the kinase activation loop Mol. Cell. Biol. 17, 2497-2501
28. Kundrapu, K., Colenberg, L., and Duhe, R. J. (2008) Activation loop tyrosines allow the JAK2(V617F) mutant to attain hyperactivation Cell Biochem. Biophys. 52, 103-112
29. Darnell, J. E., Jr., Kerr, I. M., and Stark, G. R. (1994) Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins Science 264, 1415-1421
30. Dusa, A., Staerk, J., Elliott, J., Pecquet, C., Poirel, H. A., Johnston, J. A., and Constantinescu, S. N. (2008) Substitution of pseudokinase domain residue Val-617 by large non-polar amino acids causes activation of JAK2 J. Biol. Chem. 283, 12941-12948
31. Vannucchi, A. M., Antonioli, E., Guglielmelli, P., Pardanani, A., and Tefferi, A. (2008) Clinical correlates of JAK2V617F presence or allele burden in myeloproliferative neoplasms: a critical reappraisal Leukemia 22, 1299-1307
32. Tefferi, A. (2010) Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1 Leukemia 24, 1128-1138
33. Kiss, R., Sayeski, P. P., and Keseru, G. M. (2010) Recent developments on JAK2 inhibitors: a patent review Expert Opin. Ther. Pat. 20, 471-495
34. Burley, S. K. and Petsko, G. A. (1985) Aromatic-aromatic interaction: a mechanism of protein structure stabilization Science 229, 23-28
35. Lee, T. S., Ma, W., Zhang, X., Giles, F., Kantarjian, H., and Albitar, M. (2009) Mechanisms of constitutive activation of Janus kinase 2-V617F revealed at the atomic level through molecular dynamics simulations Cancer 115, 1692-1700
36. Dusa, A., Mouton, C., Pecquet, C., Herman, M., and Constantinescu, S. N. (2010) JAK2 V617F constitutive activation requires JH2 residue F595: a pseudokinase domain target for specific inhibitors PLoS One 5, e11157
37. Staerk, J., Kallin, A., Demoulin, J. B., Vainchenker, W., and Constantinescu, S. N. (2005) JAK1 and Tyk2 activation by the homologous polycythemia vera JAK2 V617F mutation: cross-talk with IGF1 receptor J. Biol. Chem. 280, 41893-41899
38. Pardanani, A., Hood, J., Lasho, T., Levine, R. L., Martin, M. B., Noronha, G., Finke, C., Mak, C. C., Mesa, R., Zhu, H., Soll, R., Gilliland, D. G., and Tefferi, A. (2007) TG101209, a small molecule JAK2-selective kinase inhibitor potently inhibits myeloproliferative disorder-associated JAK2V617F and MPLW515L/K mutations Leukemia 21, 1658-1668
39. 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
40. Verstovsek, S., Manshouri, T., Quintas-Cardama, A., Harris, D., Cortes, J., Giles, F. J., Kantarjian, H., Priebe, W., and Estrov, Z. (2008) WP1066, a novel JAK2 inhibitor, suppresses proliferation and induces apoptosis in erythroid human cells carrying the JAK2 V617F mutation Clin. Cancer Res. 14, 788-796
41. Sayyah, J., Magis, A., Ostrov, D. A., Allan, R. W., Braylan, R. C., and Sayeski, P. P. (2008) Z3, a novel Jak2 tyrosine kinase small-molecule inhibitor that suppresses Jak2-mediated pathologic cell growth Mol. Cancer Ther. 7, 2308-2318
42. Kiss, R., Polgar, T., Kirabo, A., Sayyah, J., Figueroa, N. C., List, A. F., Sokol, L., Zuckerman, K. S., Gali, M., Bisht, K. S., Sayeski, P. P., and Keseru, G. M. (2009) Identification of a novel inhibitor of JAK2 tyrosine kinase by structure-based virtual screening Bioorg. Med. Chem. Lett. 19, 3598-3601
43. Quintas-Cardama, A., Vaddi, K., Liu, P., Manshouri, T., Li, J., Scherle, P. A., Caulder, E., Wen, X., Li, Y., Waeltz, P., Rupar, M., Burn, T., Lo, Y., Kelley, J., Covington, M., Shepard, S., Rodgers, J. D., Haley, P., Kantarjian, H., Fridman, J. S., and Verstovsek, S. (2010) Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms Blood 115, 3109-3117