Characterizing the effects of the juxtamembrane domain on vascular endothelial growth factor receptor-2 enzymatic activity, autophosphorylation, and inhibition by axitinib

Biochemistry

Volumn 48, Issue 29, 2009, Pages 7019-7031

  Solowiej, James ^a   Bergqvist, Simon ^a   McTigue, Michele A ^a   Marrone, Tami ^a   Quenzer, Terri ^a   Cobbs, Morena ^a   Ryan, Kevin ^a   Kania, Robert S ^a   Diehl, Wade ^a   Murray, Brion W ^a  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVATION LOOPS; AUTOPHOSPHORYLATION; AUTOPHOSPHORYLATION REACTION; BIOCHEMICAL CHARACTERIZATION; BIOLOGICAL FUNCTIONS; CATALYTIC DOMAINS; DISPLACEMENT METHOD; ENZYMATIC ACTIVITIES; ENZYME CONCENTRATIONS; INHIBITOR DESIGN; INTRAMOLECULAR REACTIONS; JUXTAMEMBRANE DOMAINS; MODULAR UNITS; POTENTIAL FUNCTION; PROTEIN KINASE; RECEPTOR TYROSINE KINASE; STRUCTURAL METHODS; STRUCTURAL MODELS; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR; VEGFR-2;

AMINO ACIDS; BIOLOGY; MODEL STRUCTURES; PHOSPHORYLATION;

DATA STORAGE EQUIPMENT;

AXITINIB; VASCULOTROPIN RECEPTOR 2;

ARTICLE; AUTOPHOSPHORYLATION; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME ANALYSIS; ENZYME INHIBITION; ENZYME STRUCTURE; JUXTAMEMBRANE DOMAIN; PRIORITY JOURNAL; SURFACE PLASMON RESONANCE; THERMOSTABILITY;

CALORIMETRY; CATALYTIC DOMAIN; CELL LINE; CHROMATOGRAPHY, LIQUID; GASTRINS; HUMANS; IMIDAZOLES; INDAZOLES; KINETICS; PHOSPHORYLATION; SURFACE PLASMON RESONANCE; TANDEM MASS SPECTROMETRY; VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-2;

EID: 67651232490     PISSN: 00062960     EISSN: None     Source Type: Journal    
DOI: 10.1021/bi900522y     Document Type: Article

References (56)

1. Board, R., and Jayson, G. C. (2005) Platelet-derived growth factor receptor (PDGFR): a target for anticancer therapeutics. Drug Resist. Updates 8, 75-83.
2. Fischer, B., Marinov, M., and Arcaro, A. (2007) Targeting receptor tyrosine kinase signalling in small cell lung cancer (SCLC): what have we learned so far?. Cancer Treat. Rev. 33, 391-406.
3. Sun, L., and McMahon, G. (2000) Inhibition of tumor angiogenesis by synthetic receptor tyrosine kinase inhibitors. Drug Discov. Today 5, 344-353.
4. Zwick, E., Bange, J., and Ullrich, A. (2002) Receptor tyrosine kinases as targets for anticancer drugs. Trends Mol. Med. 8, 17-23.
5. Folkman, J. (2007) Angiogenesis: an organizing principle for drug discovery?. Nat. Rev. Drug Discov. 6, 273-286.
6. Ellis, L. M., and Hicklin, D. J. (2008) VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat. Rev. 8, 579-591.
7. Roskoski, R.Jr. (2008) VEGF receptor protein-tyrosine kinases: structure and regulation. Biochem. Biophys. Res. Commun. 375, 287-291.
8. Hu-Lowe, D. D., Zou, H. Y., Grazzini, M. L., Hallin, M. E., Wickman, G. R., Amundson, K., Chen, J. H., Rewolinski, D. A., Yamazaki, S., Wu, E. Y., McTigue, M. A., Murray, B. W., Kania, R. S., O'Connor, P., Shalinsky, D. R., and Bender, S. L. (2008) Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3. Clin. Cancer Res. 14, 7272-7283.
9. Choueiri, T. K. (2008) Axitinib, a novel anti-angiogenic drug with promising activity in various solid tumors. Curr. Opin. Invest. Drugs 9, 658-671.
10. McTigue, M. A., Wickersham, J. A., Pinko, C., Showalter, R. E., Parast, C. V., Tempczyk-Russell, A., Gehring, M. R., Mroczkowski, B., Kan, C. C., Villafranca, J. E., and Appelt, K. (1999) Crystal structure of the kinase domain of human vascular endothelial growth factor receptor 2: a key enzyme in angiogenesis. Structure 7, 319-330.
11. Dougher-Vermazen, M., Hulmes, J. D., Bohlen, P., and Terman, B. I. (1994) Biological activity and phosphorylation sites of the bacterially expressed cytosolic domain of the KDR VEGF-receptor. Biochem. Biophys. Res. Commun. 205, 728-738.
12. Takahashi, T., Yamaguchi, S., Chida, K., and Shibuya, M. (2001) A single autophosphorylation site on KDR/Flk-1 is essential for VEGFA-dependent activation of PLC-gamma and DNA synthesis in vascular endothelial cells. EMBO J. 20, 2768-2778.
13. Kendall, R. L., Rutledge, R. Z., Mao, X., Tebben, A. J., Hungate, R. W., and Thomas, K. A. (1999) Vascular endothelial growth factor receptor KDR tyrosine kinase activity is increased by autophosphorylation of two activation loop tyrosine residues. J. Biol. Chem. 274, 6453-6460.
14. Dayanir, V., Meyer, R. D., Lashkari, K., and Rahimi, N. (2001) Identification of tyrosine residues in vascular endothelial growth factor receptor-2/FLK-1 involved in activation of phosphatidylinositol 3-kinase and cell proliferation. J. Biol. Chem. 276, 17686-17692.
15. Meyer, R. D., Dayanir, V., Majnoun, F., and Rahimi, N. (2002) The presence of a single tyrosine residue at the carboxyl domain of vascular endothelial growth factor receptor-2/FLK-1 regulates its autophosphorylation and activation of signaling molecules. J. Biol. Chem. 277, 27081-27087.
16. Sakurai, Y., Ohgimoto, K., Kataoka, Y., Yoshida, N., and Shibuya, M. (2005) Essential role of Flk-1 (VEGF receptor 2) tyrosine residue 1173 in vasculogenesis in mice. Proc. Natl. Acad. Sci. U.S.A. 102, 1076-1081.
17. Rahimi, N. (2006) Vascular endothelial growth factor receptors: molecular mechanisms of activation and therapeutic potentials. Exp. Eye Res. 83, 1005-1016.
18. Hubbard, S. R. (2004) Juxtamembrane autoinhibition in receptor tyrosine kinases. Nat. Rev. Mol. Cell. Biol. 5, 464-471.
19. Parast, C. V., Mroczkowski, B., Pinko, C., Misialek, S., Khambatta, G., and Appelt, K. (1998) Characterization and kinetic mechanism of catalytic domain of human vascular endothelial growth factor receptor-2 tyrosine kinase (VEGFR2 TK), a key enzyme in angiogenesis. Biochemistry 37, 16788-16801.
20. Hubbard, S. R., and Miller, W. T. (2007) Receptor tyrosine kinases: mechanisms of activation and signaling. Curr. Opin. Cell Biol. 19, 117-123.
21. Huse, M., and Kuriyan, J. (2002) The conformational plasticity of protein kinases. Cell 109, 275-282.
22. Rosnet, O., and Birnbaum, D. (1993) Hematopoietic receptors of class III receptor-type tyrosine kinases. Crit. Rev. Oncog. 4, 595-613.
23. Binns, K. L., Taylor, P. P., Sicheri, F., Pawson, T., and Holland, S. J. (2000) Phosphorylation of tyrosine residues in the kinase domain and juxtamembrane region regulates the biological and catalytic activities of Eph receptors. Mol. Cell. Biol. 20, 4791-4805.
24. Griffith, J., Black, J., Faerman, C., Swenson, L., Wynn, M., Lu, F., Lippke, J., and Saxena, K. (2004) The structural basis for autoinhibition of FLT3 by the juxtamembrane domain. Mol. Cell 13, 169-178.
25. Li, S., Covino, N. D., Stein, E. G., Till, J. H., and Hubbard, S. R. (2003) Structural and biochemical evidence for an autoinhibitory role for tyrosine 984 in the juxtamembrane region of the insulin receptor. J. Biol. Chem. 278, 26007-26014.
26. Mol, C. D., Dougan, D. R., Schneider, T. R., Skene, R. J., Kraus, M. L., Scheibe, D. N., Snell, G. P., Zou, H., Sang, B. C., and Wilson, K. P. (2004) Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase. J. Biol. Chem. 279, 31655-31663.
27. Mol, C. D., Lim, K. B., Sridhar, V., Zou, H., Chien, E. Y., Sang, B. C., Nowakowski, J., Kassel, D. B., Cronin, C. N., and McRee, D. E. (2003) Structure of a c-kit product complex reveals the basis for kinase transactivation. J. Biol. Chem. 278, 31461-31464.
28. Schubert, C., Schalk-Hihi, C., Struble, G. T., Ma, H. C., Petrounia, I. P., Brandt, B., Deckman, I. C., Patch, R. J., Player, M. R., Spurlino, J. C., and Springer, B. A. (2007) Crystal structure of the tyrosine kinase domain of colony-stimulating factor-1 receptor (cFMS) in complex with two inhibitors. J. Biol. Chem. 282, 4094-4101.
29. Backer, J. M., Kahn, C. R., Cahill, D. A., Ullrich, A., and White, M. F. (1990) Receptor-mediated internalization of insulin requires a 12-amino acid sequence in the juxtamembrane region of the insulin receptor beta-subunit. J. Biol. Chem. 265, 16450-16454.
30. Wybenga-Groot, L. E., Baskin, B., Ong, S. H., Tong, J., Pawson, T., and Sicheri, F. (2001) Structural basis for autoinhibition of the Ephb2 receptor tyrosine kinase by the unphosphorylated juxtamembrane region. Cell 106, 745-757.
31. Huse, M., Chen, Y. G., Massague, J., and Kuriyan, J. (1999) Crystal structure of the cytoplasmic domain of the type ITGF beta receptor in complex with FKBP12. Cell 96, 425-436.
32. Till, J. H., Becerra, M., Watty, A., Lu, Y., Ma, Y., Neubert, T. A., Burden, S. J., and Hubbard, S. R. (2002) Crystal structure of the MuSK tyrosine kinase: insights into receptor autoregulation. Structure 10, 1187-1196.
33. Ma, Y., Cunningham, M. E., Wang, X., Ghosh, I., Regan, L., and Longley, B. J. (1999) Inhibition of spontaneous receptor phosphorylation by residues in a putative alpha-helix in the KIT intracellular juxtamembrane region. J. Biol. Chem. 274, 13399-13402.
34. Chan, P. M., Ilangumaran, S., La Rose, J., Chakrabartty, A., and Rottapel, R. (2003) Autoinhibition of the kit receptor tyrosine kinase by the cytosolic juxtamembrane region. Mol. Cell. Biol. 23, 3067-3078.
35. Kania, R. S., Bender, S. L., Borchardt, A. J., Cripps, S. J., Hua, Y., Johnson, M. D., Theodore Otto Johnson, J., Luu, H. T., Palmer, C. L., Reich, S. H., Tempczyk-Russell, A. M., Teng, M., Thomas, C., Varney, M. D., Wallace, M. B., and Collins, M. R. (2001) Indazole compounds and pharmaceutical compositions for inhibiting protein kinases, and methods for their use, U.S. Patent 6,534,524.
36. Borchardt, A. J., Kania, R. S., and Palmer, C. L. (2003) Indazole compounds and pharmaceutical compositions for inhibiting protein kinases, and methods for their use, U.S. Patent 7,053,107.
37. Collins, M., Cripps, S., Deal, J., Kania, R. S., Lou, J., He, M., Palmer, C. L., III, W. H. R., and Zhou, R. (2003) Benzofused heterozryl amide derivatives of thienopyridines useful as therapeutic agents, pharmaceutical compositions including the same, and methods for their use, U.S. Patent 6,869,962.
38. Morrison, J. F. (1969) Kinetics of the reversible inhibition of enzyme-catalysed reactions by tight-binding inhibitors. Biochim. Biophys. Acta 185, 269-286.
39. Murphy, D. J. (2004) Determination of accurate KI values for tight-binding enzyme inhibitors: an in silico study of experimental error and assay design. Anal. Biochem. 327, 61-67.
40. Wiseman, T., Williston, S., Brandts, J. F., and Lin, L. N. (1989) Rapid measurement of binding constants and heats of binding using a new titration calorimeter. Anal. Biochem. 179, 131-137.
41. Sigurskjold, B. W. (2000) Exact analysis of competition ligand binding by displacement isothermal titration calorimetry. Anal. Biochem. 277, 260-266.
42. Morton, T. A., and Myszka, D. G. (1998) Kinetic analysis of macromolecular interactions using surface plasmon resonance bio-sensors. Methods Enzymol. 295, 268-294.
43. Copeland, R. A. (2000) Use of tight binding inhibitors to determine active enzyme concentration, in Enzymes (2nd Ed.). A Practical Introdution to Structure, Mechanism, and Data Analysis (Copeland, R. A., Ed.) pp 313-315, Wiley-VCH, New York.
44. Rich, R. L., Hoth, L. R., Geoghegan, K. F., Brown, T. A., LeMotte, P. K., Simons, S. P., Hensley, P., and Myszka, D. G. (2002) Kinetic analysis of estrogen receptor/ligand interactions. Proc. Natl. Acad. Sci. U.S.A. 99, 8562-8567.
45. Murray, B. W., Padrique, E. S., Pinko, C., and McTigue, M. A. (2001) Mechanistic effects of autophosphorylation on receptor tyrosine kinase catalysis: enzymatic characterization of Tie2 and phospho-Tie2. Biochemistry 40, 10243-10253.
46. Gotoh, N., Tojo, A., Hino, M., Yazaki, Y., and Shibuya, M. (1992) A highly conserved tyrosine residue at codon 845 within the kinase domain is not required for the transforming activity of human epidermal growth factor receptor. Biochem. Biophys. Res. Commun. 186, 768-774.
47. Cunningham, S. A., Arrate, M. P., Brock, T. A., and Waxham, M. N. (1997) Interactions of FLT-1 and KDR with phospholipase C gamma: identification of the phosphotyrosine binding sites. Biochem. Biophys. Res. Commun. 240, 635-639.
48. Greggio, E., Zambrano, I., Kaganovich, A., Beilina, A., Taymans, J. M., Daniels, V., Lewis, P., Jain, S., Ding, J., Syed, A., Thomas, K. J., Baekelandt, V., and Cookson, M. R. (2008) The Parkinson disease-associated leucine-rich repeat kinase 2 (LRRK2) is a dimer that undergoes intramolecular autophosphorylation. J. Biol. Chem. 283, 16906-16914.
49. Joseph, R. E., Fulton, D. B., and Andreotti, A. H. (2007) Mechanism and functional significance of Itk autophosphorylation. J. Mol. Biol. 373, 1281-1292.
50. Tummino, P. J., and Copeland, R. A. (2008) Residence time of receptor-ligand complexes and its effect on biological function. Biochemistry 47, 5481-5492.
51. Copeland, R. A., Pompliano, D. L., and Meek, T. D. (2006) Drug-target residence time and its implications for lead optimization. Nat. Rev. Drug Discov. 5, 730-739.
52. Ghose, A. K., Herbertz, T., Pippin, D. A., Salvino, J. M., and Mallamo, J. P. (2008) Knowledge based prediction of ligand binding modes and rational inhibitor design for kinase drug discovery. J. Med. Chem. 51, 5149-5171.
53. Hess-Stumpp, H., Haberey, M., and Thierauch, K. H. (2005) PTK 787/ZK 222584, a tyrosine kinase inhibitor of all known VEGF receptors, represses tumor growth with high efficacy. ChemBioChem 6, 550-557.
54. Amino, N., Ideyama, Y., Yamano, M., Kuromitsu, S., Tajinda, K., Samizu, K., Hisamichi, H., Matsuhisa, A., Shirasuna, K., Kudoh, M., and Shibasaki, M. (2006) YM-359445, an orally bioavailable vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor, has highly potent antitumor activity against established tumors. Clin. Cancer Res. 12, 1630-1638.
55. Bender, S.L.,Kania,R. S., and McTigue,M.A. (2004) Crystal structure of human VEGFR2 kinase domain-ligand complexes and use of the atomic coordinates in drug discovery, in WO 2004/092217 A1.
56. van der Geer, P., Hunter, T., and Lindberg, R. A. (1994) Receptor protein-tyrosine kinases and their signal transduction pathways. Annu. Rev. Cell Biol. 10, 251-337.