PDK1 and PKB/Akt: Ideal targets for development of new strategies to structure-based drug design

IUBMB Life

Volumn 55, Issue 3, 2003, Pages 117-126

  Harris, Thomas K ^a  

^a UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

Author keywords

Apoptosis; Cancer; NMR; Paramagnetic relaxation; Segmental isotopic labeling; Signal transduction; Spin label

Indexed keywords

ANTINEOPLASTIC AGENT; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4 BISPHOSPHATE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE; PHOSPHOINOSITIDE DEPENDENT KINASE 1; PLECKSTRIN; PROTEIN KINASE; PROTEIN KINASE B; UNCLASSIFIED DRUG;

BINDING SITE; CARCINOGENESIS; CELL SURVIVAL; DRUG DESIGN; DRUG TARGETING; ENZYME ACTIVATION; ENZYME ACTIVE SITE; ISOTOPE LABELING; MOLECULAR DYNAMICS; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PROTEIN BINDING; PROTEIN DOMAIN; PROTEIN PHOSPHORYLATION; PROTEIN STRUCTURE; PROTEIN TARGETING; REVIEW; SEQUENCE HOMOLOGY; SPIN LABELING; STRUCTURE ACTIVITY RELATION; X RAY CRYSTALLOGRAPHY;

ANTINEOPLASTIC AGENTS; DRUG DESIGN; MODELS, BIOLOGICAL; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-AKT; SIGNAL TRANSDUCTION; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0038809071     PISSN: 15216543     EISSN: None     Source Type: Journal    
DOI: 10.1080/1521654031000115951     Document Type: Review

References (61)

1. Hanahan, D., and Weinberg, R. A. (2000) The hallmarks of cancer. Cell 100, 57-70.
2. Duesberg, P., and Rasnick, D. (2000) Aneuploidy, the somatic mutation that makes cancer a species of its own. Cell Motil. Cytoskeleton 47, 81-107.
3. Cahill, D. P., Kinzler, K. W., Vogelstein, B., and Lengauer, C. (1999) Genetic instability and Darwinian selection in tumours. Trends Cell Biol. 9, M57-60.
4. Druker, B. J. (2002) STI571 (Gleevec™) as a paradigm for cancer therapy. Trends Mol. Med. 8, S14-S18.
5. Parker, P. J., and Parkinson, S. J. (2001) AGC protein kinases phosphorylation and protein kinase C. Biochem. Soc. Trans. 29, 860-863.
6. Lee, J. T., McCubrey, J. A. (2002) The Raf/MEK/ERK signal transduction cascade as a target for chemotherapeutic intervention in leukemia. Leukemia 16, 486-507.
7. Herzig, M., and Christofori, G. (2002) Recent advances in cancer research: mouse models of tumorigenesis. Biochim Biophys Acta 1602, 97-113.
8. Schlessinger, J. (2000) Cell signaling by receptor tyrosine kinases. Cell 103, 211-225.
9. Cantley, L. (2002) The phosphatidylinositol 3-Kinase Pathway. Science 296, 1655-1657.
10. Maehama, T., and Dixon, J. E. (1998) The tumor suppressor, PTEN/ Mmac1, dephosphorylates the lipid second messanger, phosphatidylinositol 3,4,5-triphosphate. J. Biol. Chem. 273, 13375-13378.
11. Leslie, N. R., and Downes, C. P. (2002) PTEN: the down side of PI 3kinase signalling. Cell. Signal. 14, 285-295.
12. Blume-Jensen, P., and Hunter, T. (2001) Oncogenic kinase signalling Nature 411, 355-365.
13. Alessi, D. R., James, S. R., Downes, C. P., Holmes, A. B., Gaffney, P. R. J., Reese, C. B., and Cohen, P. (1997) Characterization of a 3phosphoinositide-dependent protein kinase Bα. Curr. Biol. 7, 261-269.
14. Alessi, D. R., Deak, M., Casamayor, A., Caudwell, F. B., Morrice, N., Norman, D. G., Gaffney, P., Reese, C. B., MacDougall, C. N., Harbison, D., Ashworth, A., and Bownes, M. (1997) 3-Phosphoinositide-dependent protein kinase-1 (PDKI): Structural and functional homology with the Drosphila DSTPK61 kinase. Curr. Biol. 7, 776-789.
15. Anderson, K. E., Coadwell, J., Stephens, L. R., and Hawkins, P. T. (1998) Translocation of PDK-1 to the plasma membrane is important in allowing PDK-1 to activate protein kinase B. Curr. Biol. 8, 684-691.
16. Franke, T. F., Kaplan, D. R., Cantley, L. C., and Toker, A. (1997) Direct regulation of the Akt proto-oncogene product by phosphatidylinositol-3,4-bisphosphate. Science 275, 665-668.
17. Frech, M., Andjelkovic, M., Ingley, E., Reddy, K. K., Falck, J. R., and Hemmings, B. A. (1997) High-affinity binding of inositol phosphates and phosphoinositides to the pleckstrin homology domain of RAC/protein kinase B and their influence on kinase activity. J. Biol. Chem 272, 8474-8481.
18. Lawlor, M. A., and Alessi, D. R. (2001) PKB/Akt: a key mediator of cell proliferation, survival, and insulin responses? J. Cell Science 114, 2903-2910.
19. Leslie, N. R., Biondi, R. M., and Alessi, D. R. (2001) Phosphoinositide-regulated kinases and phosphoinositide phosphatases. Chem. Rev. 101, 2365-2380.
20. Alessi, D. R., Andjelkovic, M., Caudwell, B. F., Cron, P., Morrice, N., Cohen, P., and Hemmings, B. A. (1996) Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J. 15, 6541-6551.
21. Toker, A., and Newton, A. C. (2000) Cellular signaling: pivoting around PDK-1. Cell 103, 185-188.
22. Stokoe, D., Stephens, L. R., Copeland, T., Gaffney, P R., Reese, C. B., Painter, G. F., Holmes, A. B., McCormick, F., and Hawkins, P. T. (1997) Dual role of phosphatidylinositol-3,4,5-triphosphate in the activation of protein kinase B. Science 277, 567-570.
23. Filippa, N., Sable, C. L., Hemmings, B. A., and Van Obberghen, E. (2000) Effect of phosphoinositide-dependent kinase 1 on protein kinase B translocation and its subsequent activation. Mol. Cell. Biol. 20, 5712-5721.
24. Stephens, L., Anderson, K., Stokoe, D., Erdjument-Bromage, H., Painter, G. F., Holmes, A. B., Gaffney, P. R. J., Reese, C. B., McCormick, F., Tempst, P., et al. (1998) Protein kinase B kinases that mediate phosphatidylinositol 3,4,5-triphosphate-dependent activation of protein kinase B. Science 279, 710-714.
25. Casamayor, A., Morrice, N. A., and Alessi, D. R. (1999) Phosphorylation of ser-241 is essential for the activity of 3-phosphoinositidedependent protein kinase-1: identification of five sites of phosphorylation in vivo. Biochem. J. 342, 287-292.
26. Hill, M. M., and Hemmings, B. A. (2002) Inhibition of protein kinase B/Akt: implications for cancer therapy. Pharm. Therapeutics 93, 243-251.
27. Nicholson, K. M., and Anderson, N. G. (2002) The protein kinase B/Akt signalling pathway in human malignancy. Cell. Signal. 14, 381-395.
28. Hill, M. M., Andjelkovic, M., Brazil, D. P., Ferrari, S., Fabbro, D., and Hemmings, B. A. (2001) Insulin-stimulated protein kinase B phosphorylation on ser-473 is independent of its activity and occurs through a staurosporine-insensitive kinase. J. Biol. Chem 276, 25643-25646.
29. Cohen, P. (2002) Protein kinases-the major drug targets of the twenty-first century? Nat. Rev. Drug Discov. 1, 309-315.
30. Kahan, B. D. (2002) The limitations of calcineurin and mTOR inhibitors: new directions for immunosuppressive strategies. Transplant Proc. 34, 130-133.
31. Cohen, P. (1999) The development and therapeutic potential of protein kinase inhibitors. Curr. Opin. Chem. Biol. 3, 459-465.
32. Davies, S. P., Reddy, H., Caivano, M., and Cohen, P. (2000) Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem. J. 351, 95-105.
33. Tong, L. Pav, S., White, D. M., Rogers, S., Crane, K. M., Cywin, C. L., Brown, M. L., Pargellis, C. A. (1997) A highly specific inhibitor of human p38 MAP kinase binds in the ATP pocket. Nat. Struct. Biol. 4, 311-316.
34. Jencks, W. P. (1981) On the attribution and additivity of binding energies. Proc. Natl. Acad. Sci USA 78, 4046-4050.
35. Parang, K., Till, J. H., Ablooglu, A. J., Kohanski, R. A., Hubbard, S. R., and Cole, P. A. (2001) Mechanism-based design of a protein kinase inhibitor. Nat. Struct. Biol. 8, 37-41.
36. Biondi, R. M., Komander, D., Thomas, C. C., Lizcano, J. M., Deak, M., Alessi, D. R., and van Aalten, D. M. F. (2002) High resolution crystal structure of the human PDK1 catalytic domain defines the regulatory phosphopeptide docking site. EMBO J. 21, 4219-4228.
37. Yang, J., Cron, P., Good, V. M., Thompson, V., Hemmings, B. A., and Barford, D. (2002) Crystal structure of an activated Akt/Protein Kinase B ternary complex with GSK3-peptide and AMP-PNP. Nature Struct. Biol. 9, 940-944.
38. Fruman, D. A., Rameh, L. E., and Cantley, L. C. (1999) Phosphoinositide binding domains: embracing 3-phosphate. Cell 97, 817-820.
39. Rebecchi, M. J., and Scarlata, S. (1998) Pleckstrin homology domains: a common fold with diverse functions. Annu. Rev. Biophys. Biomol. Struct. 27, 503-528.
40. Ferguson, K. M., Kavran, J. M., Sankaran, V. G., Fournier, E., Isakoff, S. J., Skolnik, E. Y., and Lemmon, M. A. (2000) Structural basis for discrimination of 3-phosphoinositides by pleckstrin homology domains. Mol. Cell 6, 373-384.
41. Thomas, C. C., Deak, M., Alessi, D. R., and van Aalten, D. M. F. (2002) High-resolution structure of the pleckstrin homology domain of protein kinase B/Akt bound to phosphatidylinositol (3,4,5)triphosphate. Curr. Biol. 12, 1256-1262.
42. Biondi, R. M., Kieloch, A., Currie, R. A., Deak, M., and Alessi, D. R. (2001) The PIF-binding pocket in PDKI is essential for activation of S6K and SGK, but not PKB. EMBO J. 20, 4380-4390.
43. Xu, R., Ayers, B., Cowburn, D., and Muir, T. W. (1999) Chemical ligation of folded recombinant proteins: segmental isotope labeling of domains for NMR studies. Proc. Natl. Acad. Sci. 96, 388-393.
44. Camarero, J. A., Shekhtman, A., Campbell, E. A., Chlenov, M., Gruber, T. M., Bryant, D. A., Darst, S. A., and Muir, T. W. (2002) Autoregulation of a bacterial σ factor explored by using segmental isotope labeling and NMR. Proc. Natl. Acad. Sci. 99, 8536-8541.
45. Otomo, T., Ito, N., Kyogku, Y., and Yamazaki, T. (1999) MR observation of selected segments in a larger protein: central segment isotope labeling through intein-mediated ligation. Biochemistry 38, 16040-16044.
46. Yamazaki, T., Otomo, T., Oda, N., Kyogoku, Y., Uegaki, K., Ito, N., Ishino, Y., and Nakamura, H. (1998) Segmental isotope labeling for protein NMR using peptide splicing. J. Am. Chem. Soc. 120, 5591-5592.
47. Solomon, I. (1955) Relaxation processes in a system of two spins. Phys. Rev. 99, 559-565.
48. Mildvan, A. S., and Weiner, H. (1969) Interaction of a spin-labeled analogue of nicotinamide adenine dinucleotide with alcohol dehydrogenase. J. Biol. Chem. 244, 2465-2475.
49. Mildvan, A. S. (1996) Enzymes utilizing ATP: kinases, ATPases and polymerases. In Encyclopedia of NMR. pp. 1909-1918. Chichester, UK, Wiley & Sons Ltd.
50. Mildvan, A. S. (1997) Mechanisms of signaling and related enzymes. Proteins: Struct., Func., and Gen. 29, 401-416.
51. 1H NMR of three spin-labeled derivatives of bovine pancreatic trypsin inhibitor. Biochemistry 25, 2356-2364.
52. Gaponenko, V., Howarth, J. W., Columbus, L., Gasmi-Seabrook, G., Yuan, J., Hubbell, W. L., and Rosevear, P. R. (2000) Protein global fold determination using site-directed spin and isotope labeling. Protein Sci. 9, 302-309.
53. Battiste, J. L. and Wagner, G. (2000) Utilization of site-directed spin labeling and high resolution heteronuclear nuclear magnetic resonance for global fold determination of large proteins with limited nuclear Overhauser effect data. Biochemistry 39, 5355-5365.
54. Mildvan, A. S., and Gupta, R. K. (1978) Nuclear relaxation measurements of the geometry of enzyme-bound substrates and analogs. Methods Enzymol. 49G, 322-359.
55. Krugh, T. R. (1979) Spin-label-induced nuclear magnetic resonance relaxation studies of enzymes. In Spin Labeling. II. Theory and Applications (Berliner L., ed.), pp. 339-372, Academic Press New York.
56. Brünger, A. T. (1992) X-PLOR (Version 3.1), A System for X-ray Crystallography and NMR, Yale University Press, New Haven, CT.
57. Martin, S. L., Vrhovski, B., and Weiss, A. S. (1995) Total synthesis and expression in Echerichia coli of a gene encoding human tropoelastin. Gene 154, 159-166.
58. Jaffe, E. K., Volin, M., Bronson-Mullins, C. R., Dunbrack, Jr., R. L., Kervinen, J., Martins, J., Quinlin, Jr., J. F., Sazinski, M. H., Steinhouse, E. M., and Yeung, A. T. (2000) An artificial gene for human porphobilinogen synthase allows comparison of an allelic variation implicated in susceptibility to lead poisoning. J. Biol. Chem. 275, 2619-2626.
59. Rehm, B. H. A., Qi, Q., Beerman, Br. B., Hinz, H.-J., Steinbüchel, A. (2001) Matrix-assisted in vitro refolding of Pseudomonas aeruginosa class II polyhydroxyalkonate synthase from inclusion bodies produced in recombinant Escherichia coli. Biochem. J. 358, 263-268.
60. Gupta, R. K., Fung, C. H., and Mildvan, A. S. (1976) Chromium(III)adenosine triphosphate as a paramagnetic probe to determine intersubstrate distances on pyruvate kinase. J. Biol. Chem. 251, 2421-2430.
61. Granot, J., Mildvan, A. S., Bramson, H. N., and Kaiser, E. T. (1980) Magnetic resonance measurements of intersubstrate distances at the active site of protein kinase using substitution-inert cobalt(III) and chromium(III) complexes of adenosine 5(-(β,γ-methylenetriphosphate). Biochemistry 19, 3537-3543.