Activation of tyrosine kinases by mutation of the gatekeeper threonine

Nature Structural and Molecular Biology

Volumn 15, Issue 10, 2008, Pages 1109-1118

  Azam, Mohammad ^a,b,c   Seeliger, Markus A ^d   Gray, Nathanael S ^b,c,e   Kuriyan, John ^d   Daley, George Q ^a,b,e,f,g  

^a BOSTON CHILDREN S HOSPITAL   (United States)

^b DANA FARBER CANCER INSTITUTE   (United States)

^c HARVARD MEDICAL SCHOOL   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e Seeley G Mudd Building ^*  (United States)

^f BRIGHAM AND WOMEN S HOSPITAL   (United States)

^g HARVARD STEM CELL INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

6 (2,6 DICHLOROPHENYL) 2 [3 (HYDROXYMETHYL)ANILINO] 8 METHYLPYRIDO[2,3 D]PYRIMIDIN 7(8H) ONE; ABELSON KINASE; BCR ABL PROTEIN; EPIDERMAL GROWTH FACTOR RECEPTOR; GLYCINE; IMATINIB; NILOTINIB; PLATELET DERIVED GROWTH FACTOR ALPHA RECEPTOR; PLATELET DERIVED GROWTH FACTOR BETA RECEPTOR; PROTEIN TYROSINE KINASE; THREONINE;

AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; ARTICLE; CELL TRANSFORMATION; CONTROLLED STUDY; DRUG INHIBITION; DRUG MECHANISM; ENZYME ACTIVATION; ENZYME ANALYSIS; ENZYME CONFORMATION; ENZYME STRUCTURE; GENE MUTATION; HUMAN; HUMAN CELL; HYDROPHOBICITY; MOUSE; MUTAGENESIS; NONHUMAN; ONCOGENE SRC; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN INTERACTION; PROTEIN PHOSPHORYLATION;

BINDING SITES; CELL LINE; CRYSTALLOGRAPHY, X-RAY; ENZYME ACTIVATION; HUMANS; HYDROPHOBICITY; MODELS, MOLECULAR; MUTATION; PROTEIN STRUCTURE, TERTIARY; PROTEIN-TYROSINE KINASES; PROTO-ONCOGENE PROTEINS C-ABL; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECEPTORS, PLATELET-DERIVED GROWTH FACTOR; THREONINE;

PYRONIA TITHONUS;

EID: 53549104402     PISSN: 15459993     EISSN: 15459985     Source Type: Journal    
DOI: 10.1038/nsmb.1486     Document Type: Article

References (57)

1. Cohen, P. Protein kinases - the major drug targets of the twenty-first century? Nat. Rev. Drug Discov. 1, 309-315 (2002).
2. Dibb, N.J., Dilworth, S.M. & Mol, C.D. Switching on kinases: oncogenic activation of BRAF and the PDGFR family. Nat. Rev. Cancer 4, 718-727 (2004).
3. Sawyers, C. Targeted cancer therapy. Nature 432, 294-297 (2004).
4. Sawyers, C.L. Opportunities and challenges in the development of kinase inhibitor therapy for cancer. Genes Dev. 17, 2998-3010 (2003).
5. Noble, M.E., Endicott, J.A. & Johnson, L.N. Protein kinase inhibitors: insights into drug design from structure. Science 303, 1800-1805 (2004).
6. Liu, Y., Shah, K., Yang, F., Witucki, L. & Shokat, K.M. A molecular gate which controls unnatural ATP analogue recognition by the tyrosine kinase v-Src. Bioorg. Med. Chem. 6, 1219-1226 (1998).
7. Azam, M. & Daley, G.Q. Anticipating clinical resistance to target-directed agents: the BCR-ABL paradigm. Mol. Diagn. Ther. 10, 67-76 (2006).
8. Daub, H., Specht, K. & Ullrich, A. Strategies to overcome resistance to targeted protein kinase inhibitors. Nat. Rev. Drug Discov. 3, 1001-1010 (2004).
9. Druker, B.J. et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat. Med. 2, 561-566 (1996).
10. Heinrich, M.C., Blanke, C.D., Druker, B.J. & Corless, C.L. Inhibition of KIT tyrosine kinase activity: a novel molecular approach to the treatment of KIT-positive malignancies. J. Clin. Oncol. 20, 1692-1703 (2002).
11. Buchdunger, E. et al. Abl protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-kit and platelet-derived growth factor receptors. J. Pharmacol. Exp. Ther. 295, 139-145 (2000).
12. Cools, J. et al. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N. Engl. J. Med. 348, 1201-1214 (2003).
13. Gorre, M.E. et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 293, 876-880 (2001).
14. Shah, N.P. et al. Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemia. Cancer Cell 2, 117-125 (2002).
15. Tamborini, E. et al. A new mutation in the KIT ATP pocket causes acquired resistance to imatinib in a gastrointestinal stromal tumor patient. Gastroenterology 127, 294-299 (2004).
16. Cools, J. et al. PKC412 overcomes resistance to imatinib in a murine model of FIP1L1-PDGFRα-induced myeloproliferative disease. Cancer Cell 3, 459-469 (2003).
17. Kobayashi, S. et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 352, 786-792 (2005).
18. Bell, D.W. et al. Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR. Nat. Genet. 37, 1315-1316 (2005).
19. Levinson, N.M. et al. A Src-like inactive conformation in the Abl tyrosine kinase domain. PLoS Biol. 4, e144 (2006).
20. Harrison, S.C. Variation on an Src-like theme. Cell 112, 737-740 (2003).
21. Azam, M., Latek, R.R. & Daley, G.Q. Mechanisms of autoinhibition and STI-571/ imatinib resistance revealed by mutagenesis of BCR-ABL. Cell 112, 831-843 (2003).
22. Nagar, B. et al. Structural basis for the autoinhibition of c-Abl tyrosine kinase. Cell 112, 859-871 (2003).
23. Hantschel, O. et al. A myristoyl/phosphotyrosine switch regulates c-Abl. Cell 112, 845-857 (2003).
24. Xu, W., Harrison, S.C. & Eck, M.J. Three-dimensional structure of the tyrosine kinase c-Src. Nature 385, 595-602 (1997).
25. Sicheri, F., Moarefi, I. & Kuriyan, J. Crystal structure of the Src family tyrosine kinase Hck. Nature 385, 602-609 (1997).
26. Moarefi, I. et al. Activation of the Src-family tyrosine kinase Hck by SH3 domain displacement. Nature 385, 650-653 (1997).
27. Takeya, T. & Hanafusa, H. Structure and sequence of the cellular gene homologous to the RSV src gene and the mechanism for generating the transforming virus. Cell 32, 881-890 (1983).
28. Hunter, T. A tail of two src's: Mutatis mutandis. Cell 49, 1-4 (1987).
29. Kato, J.Y. et al. Amino acid substitutions sufficient to convert the nontransforming p60c-src protein to a transforming protein. Mol. Cell. Biol. 6, 4155-4160 (1986).
30. Azam, M. et al. Activity of dual SRC-ABL inhibitors highlights the role of BCR/ABL kinase dynamics in drug resistance. Proc. Natl. Acad. Sci. USA 103, 9244-9249 (2006).
31. Kornev, A.P., Haste, N.M., Taylor, S.S. & Eyck, L.F. Surface comparison of active and inactive protein kinases identifies a conserved activation mechanism. Proc. Natl. Acad. Sci. USA 103, 17783-17788 (2006).
32. Daley, G.Q. & Baltimore, D. Transformation of an interleukin 3-dependent hematopoietic cell line by the chronic myelogenous leukemia-specific P210bcr/abl protein. Proc. Natl. Acad. Sci. USA 85, 9312-9316 (1988).
33. Koh, E.Y., Chen, T. & Daley, G.Q. Genetic complementation of cytokine signaling identifies central role of kinases in hematopoietic cell proliferation. Oncogene 23, 1214-1220 (2004).
34. Carroll, M., Tomasson, M.H., Barker, G.F., Golub, T.R. & Gilliland, D.G. The TEL/platelet-derived growth factor β receptor (PDGFβR) fusion in chronic myelomonocytic leukemia is a transforming protein that self-associates and activates PDGFβR kinase-dependent signaling pathways. Proc. Natl. Acad. Sci. USA 93, 14845-14850 (1996).
35. Mizuki, M. et al. Flt3 mutations from patients with acute myeloid leukemia induce transformation of 32D cells mediated by the Ras and STAT5 pathways. Blood 96, 3907-3914 (2000).
36. Jiang, J. et al. Epidermal growth factor-independent transformation of Ba/F3 cells with cancer-derived epidermal growth factor receptor mutants induces gefitinib-sensitive cell cycle progression. Cancer Res. 65, 8968-8974 (2005).
37. Levine, R.L. et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell 7, 387-397 (2005).
38. Mathey-Prevot, B., Nabel, G., Palacios, R. & Baltimore, D. Abelson virus abrogation of interleukin-3 dependence in a lymphoid cell line. Mol. Cell. Biol. 6, 4133-4135 (1986).
39. Huse, M. & Kuriyan, J. The conformational plasticity of protein kinases. Cell 109, 275-282 (2002).
40. Yun, C.H. et al. Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity. Cancer Cell 11, 217-227 (2007).
41. Zhang, X., Gureasko, J., Shen, K., Cole, P.A. & Kuriyan, J. An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor. Cell 125, 1137-1149 (2006).
42. Okram, B. et al. A general strategy for creating "inactive-conformation" Abl inhibitors. Chem. Biol. 13, 779-786 (2006).
43. O'Hare, T. et al. 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 (2005).
44. Schindler, T. et al. Structural mechanism for STI-571 inhibition of abelson tyrosine kinase. Science 289, 1938-1942 (2000).
45. Pfeifer, H. et al. Kinase domain mutations of BCR-ABL frequently precede imatinibbased therapy and give rise to relapse in patients with de novo Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood 110, 727-734 (2007).
46. Skaggs, B.J. et al. Phosphorylation of the ATP-binding loop directs oncogenicity of drug-resistant BCR-ABL mutants. Proc. Natl. Acad. Sci. USA 103, 19466-19471 (2006).
47. Griswold, I.J. et al. Kinase domain mutants of Bcr-Abl exhibit altered transformation potency, kinase activity, and substrate utilization, irrespective of sensitivity to imatinib. Mol. Cell. Biol. 26, 6082-6093 (2006).
48. Corbin, A.S., Buchdunger, E., Pascal, F. & Druker, B.J. Analysis of the structural basis of specificity of inhibition of the Abl kinase by STI571. J. Biol. Chem. 277, 32214-32219 (2002).
49. Yun, C.H. et al. The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP. Proc. Natl. Acad. Sci. USA 105, 2070-2075 (2008).
50. Emrick, M.A. et al. The gatekeeper residue controls autoactivation of ERK2 via a pathway of intramolecular connectivity. Proc. Natl. Acad. Sci. USA 103, 18101-18106 (2006).
51. Li, S., Ilaria, R.L. Jr, Million, R.P., Daley, G.Q. & Van Etten, R.A. The P190, P210, and P230 forms of the BCR/ABL oncogene induce a similar chronic myeloid leukemia-like syndrome in mice but have different lymphoid leukemogenic activity. J. Exp. Med. 189, 1399-1412 (1999).
52. Seeliger, M.A. et al. c-Src binds to the cancer drug imatinib with an inactive Abl/c-Kit conformation and a distributed thermodynamic penalty. Structure 15, 299-311 (2007).
53. Otwinowski, Z. & Minor, W. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276, 307-326 (1997).
54. McCoy, A.J., Grosse-Kunstleve, R.W., Storoni, L.C. & Read, R.J. Likelihood-enhanced fast translation functions. Acta Crystallogr. D Biol. Crystallogr. 61, 458-464 (2005).
55. Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60, 2126-2132 (2004).
56. Afonine, P.V., Grosse-Kunstleve, R.W. & Adams, P.D. A robust bulk-solvent correction and anisotropic scaling procedure. Acta Crystallogr. D Biol. Crystallogr. 61, 850-855 (2005).
57. Murshudov, G.N., Vagin, A.A. & Dodson, E.J. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D Biol. Crystallogr. 53, 240-255 (1997).