Adenosine-binding motif mimicry and cellular effects of a thieno[2,3-d]pyrimidine-based chemical inhibitor of atypical protein kinase C isoenzymes

Biochemical Journal

Volumn 451, Issue 2, 2013, Pages 329-342

  Kjaeær, Svend ^a   Linch, Mark ^a   Purkiss, Andrew ^a   Kostelecky, Brenda ^a   Knowles, Phillip P ^a   Rosse, Carine ^a   Riou, Philippe ^a   Soudy, Christelle ^b   Kaye, Sarah ^b   Patel, Bhavisha ^b   Soriano, Erika ^a   Murray Rust, Judith ^a   Barton, Caroline ^b   Dillon, Christian ^b   Roffey, Jon ^b   Parker, Peter J ^a,c   Mcdonald, Neil Q ^d  

^a IMPERIAL CANCER RESEARCH FUND   (United Kingdom)

^b UNIVERSITY COLLEGE LONDON   (United Kingdom)

^c KING'S COLLEGE LONDON   (United Kingdom)

^d UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

ATP pocket; Atypical protein kinase C; Cell migration; Cell polarity; Cell based assay; Chemical inhibitor; Crystallography; Madin Darby canine kidney (MDCK) cell; Protein kinase A protein kinase G protein kinase C family kinase (AGC kinase)

Indexed keywords

ADENOSINE TRIPHOSPHATE; CRT 0066854; PROTEIN KINASE C INHIBITOR; PROTEIN KINASE C IOTA; PROTEIN KINASE C ZETA; THIENO[2,3 D]PYRIMIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ACIDITY; ARTICLE; CELL ASSAY; CELL MIGRATION; CELL VIABILITY; COLONY FORMATION; CRYSTAL STRUCTURE; DOSE RESPONSE; EMBRYO; ENZYME ACTIVITY; HUMAN; HUMAN CELL; HUMAN TISSUE; HYDROGEN BOND; HYDROPHOBICITY; IC 50; IN VITRO STUDY; LIPOPHILICITY; MOLECULAR MIMICRY; PHENOTYPE; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DOMAIN; PROTEIN MOTIF; PROTEIN PHOSPHORYLATION;

ADENOSINE; ADENOSINE TRIPHOSPHATE; AMINO ACID SEQUENCE; ANIMALS; BINDING SITES; CELL LINE; CELL MOVEMENT; CELL SURVIVAL; CRYSTALLOGRAPHY, X-RAY; CYTOSKELETAL PROTEINS; DOGS; DRUG EVALUATION, PRECLINICAL; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; INHIBITORY CONCENTRATION 50; ISOENZYMES; MOLECULAR MIMICRY; MOLECULAR SEQUENCE DATA; PHOSPHORYLATION; PROTEIN KINASE C; PROTEIN KINASE INHIBITORS; PYRIMIDINES; THIOPHENES;

EID: 84875617207     PISSN: 02646021     EISSN: 14708728     Source Type: Journal    
DOI: 10.1042/BJ20121871     Document Type: Article

References (51)

1. Bosco, R., Melloni, E., Celeghini, C., Rimondi, E., Vaccarezza, M. and Zauli, G. (2011) Fine tuning of protein kinase C (PKC) isoforms in cancer: shortening the distance from the laboratory to the bedside. Mini-Rev. Med. Chem. 11, 185-199
2. Rosse, C., Linch, M., Kermorgant, S., Cameron, A. J., Boeckeler, K. and Parker, P. J. (2010) PKC and the control of localized signal dynamics. Nat. Rev. Mol. Cell Biol. 11, 103-112
3. Parker, P. J. and Murray-Rust, J. (2004) PKC at a glance. J. Cell Sci. 117, 131-132
4. Pearce, L. R., Komander, D. and Alessi, D. R. (2010) The nuts and bolts of AGC protein kinases. Nat. Rev. Mol. Cell Biol. 11, 9-22
5. Suzuki, A., Akimoto, K. and Ohno, S. (2003) Protein kinase C λ/ι (PKCλ/ι): a PKC isotype essential for the development of multicellular organisms. J. Biochem. 133, 9-16
6. Knoblich, J. A. (2010) Asymmetric cell division: recent developments and their implications for tumour biology. Nat. Rev. Mol. Cell Biol. 11, 849-860
7. Suzuki, A. and Ohno, S. (2006) The PAR-aPKC system: lessons in polarity. J. Cell Sci. 119, 979-987
8. Hao, Y., Du, Q., Chen, X., Zheng, Z., Balsbaugh, J. L., Maitra, S., Shabanowitz, J., Hunt, D. F. and Macara, I. G. (2010) Par3 controls epithelial spindle orientation by aPKC-mediated phosphorylation of apical Pins. Curr. Biol. 20, 1809-1818
9. Durgan, J., Kaji, N., Jin, D. and Hall, A. (2011) Par6B and atypical PKC regulate mitotic spindle orientation during epithelial morphogenesis. J. Biol. Chem. 286, 12461-12474
10. Rosse, C., Formstecher, E., Boeckeler, K., Zhao, Y., Kremerskothen, J., White, M. D., Camonis, J. H. and Parker, P. J. (2009) An aPKC-Exocyst complex controls paxillin phosphorylation and migration through localised JNK1 activation. PLoS Biol. 7, e1000235
11. Etienne-Manneville, S. and Hall, A. (2003) Cell polarity: Par6, aPKC and cytoskeletal crosstalk. Curr. Opin. Cell Biol. 15, 67-72
12. Fields, A. P. and Regala, R. P. (2007) Protein kinase C iota: human oncogene, prognostic marker and therapeutic target. Pharmacol. Res. 55, 487-497
13. Guo, H., Gu, F., Li, W., Zhang, B., Niu, R., Fu, L., Zhang, N. and Ma, Y. (2009) Reduction of protein kinase C ζ inhibits migration and invasion of human glioblastoma cells. J. Neurochem. 109, 203-213
14. Liu, Y., Wang, B., Wang, J., Wan, W., Sun, R., Zhao, Y. and Zhang, N. (2009) Down-regulation of PKCζ expression inhibits chemotaxis signal transduction in human lung cancer cells. Lung Cancer 63, 210-218
15. Sun, R., Gao, P., Chen, L., Ma, D., Wang, J., Oppenheim, J. J. and Zhang, N. (2005) Protein kinase C ζ is required for epidermal growth factor-induced chemotaxis of human breast cancer cells. Cancer Res. 65, 1433-1441
16. Xu, L. and Deng, X. (2006) Protein kinase Cι promotes nicotine-induced migration and invasion of cancer cells via phosphorylation of μ- and m-calpains. J. Biol. Chem. 281, 4457-4466
17. Regala, R. P., Weems, C., Jamieson, L., Copland, J. A., Thompson, E. A. and Fields, A. P. (2005) Atypical protein kinase Cι plays a critical role in human lung cancer cell growth and tumorigenicity. J. Biol. Chem. 280, 31109-31115
18. Aranda, V., Haire, T., Nolan, M. E., Calarco, J. P., Rosenberg, A. Z., Fawcett, J. P., Pawson, T. and Muthuswamy, S. K. (2006) Par6-aPKC uncouples ErbB2 induced disruption of polarized epithelial organization from proliferation control. Nat. Cell Biol. 8, 1235-1245
19. Brumby, A. M. and Richardson, H. E. (2003) scribble mutants cooperate with oncogenic Ras or Notch to cause neoplastic overgrowth in Drosophila. EMBO J. 22, 5769-5779
20. Pagliarini, R. A. and Xu, T. (2003) A genetic screen in Drosophila for metastatic behavior. Science 302, 1227-1231
21. Duran, A., Linares, J. F., Galvez, A. S., Wikenheiser, K., Flores, J. M., Diaz-Meco, M. T. and Moscat, J. (2008) The signaling adaptor p62 is an important NF-κB mediator in tumorigenesis. Cancer Cell 13, 343-354
22. Regala, R. P., Davis, R. K., Kunz, A., Khoor, A., Leitges, M. and Fields, A. P. (2009) Atypical protein kinase C ι is required for bronchioalveolar stem cell expansion and lung tumorigenesis. Cancer Res. 69, 7603-7611
23. Yang, Y. L., Chu, J. Y., Luo, M. L., Wu, Y. P., Zhang, Y., Feng, Y. B., Shi, Z. Z., Xu, X., Han, Y. L., Cai, Y. et al. (2008) Amplification of PRKCI, located in 3q26, is associated with lymph node metastasis in esophageal squamous cell carcinoma. Genes, Chromosomes Cancer 47, 127-136
24. Kojima, Y., Akimoto, K., Nagashima, Y., Ishiguro, H., Shirai, S., Chishima, T., Ichikawa, Y., Ishikawa, T., Sasaki, T., Kubota, Y. et al. (2008) The overexpression and altered localization of the atypical protein kinase C λ/ι in breast cancer correlates with the pathologic type of these tumors. Hum. Pathol. 39, 824-831
25. Scotti, M. L., Bamlet, W. R., Smyrk, T. C., Fields, A. P. and Murray, N. R. (2010) Protein kinase Cι is required for pancreatic cancer cell transformed growth and tumorigenesis. Cancer Res. 70, 2064-2074
26. Takagawa, R., Akimoto, K., Ichikawa, Y., Akiyama, H., Kojima, Y., Ishiguro, H., Inayama, Y., Aoki, I., Kunisaki, C., Endo, I. et al. (2010) High expression of atypical protein kinase C λ/ι in gastric cancer as a prognostic factor for recurrence. Ann. Surg. Oncol. 17, 81-88
27. Li, Q., Wang, J. M., Liu, C., Xiao, B. L., Lu, J. X. and Zou, S. Q. (2008) Correlation of aPKC-ι and E-cadherin expression with invasion and prognosis of cholangiocarcinoma. Hepatobiliary Pancreatic Dis. Int. 7, 70-75
28. Patel, R., Win, H., Desai, S., Patel, K., Matthews, J. A. and Acevedo-Duncan, M. (2008) Involvement of PKC-ι in glioma proliferation. Cell Proliferation 41, 122-135
29. Murray, N. R. and Fields, A. P. (1997) Atypical protein kinase C ι protects human leukemia cells against drug-induced apoptosis. J. Biol. Chem. 272, 27521-27524
30. Baldwin, R. M., Garratt-Lalonde, M., Parolin, D. A., Krzyzanowski, P. M., Andrade, M. A. and Lorimer, I. A. (2006) Protection of glioblastoma cells from cisplatin cytotoxicity via protein kinase Cι -mediated attenuation of p38 MAP kinase signaling. Oncogene 25, 2909-2919
31. Jin, Y. T., Ying, X. X., Hu, Y. H., Zou, Q., Wang, H. Y. and Xu, Y. H. (2008) aPKC inhibitors might be the sensitizer of chemotherapy and adoptive immunotherapy in the treatment of hASIPa-overexpressed breast cancer. Oncol. Res. 17, 59-68
32. Kikuchi, K., Soundararajan, A., Zarzabal, L. A., Weems, C. R., Nelon, L. D., Hampton, S. T., Michalek, J. E., Rubin, B. P., Fields, A. P. and Keller, C. (2012) Protein kinase C ι as a therapeutic target in alveolar rhabdomyosarcoma. Oncogene 32, 286-95
33. Knight, Z. A. and Shokat, K. M. (2005) Features of selective kinase inhibitors. Chem. Biol. 12, 621-637
34. Roffey, J., Rosse, C., Linch, M., Hibbert, A., McDonald, N. Q. and Parker, P. J. (2009) Protein kinase C intervention: the state of play. Curr. Opin. Cell Biol. 21, 268-279
35. Frohner, W., Lopez-Garcia, L. A., Neimanis, S., Weber, N., Navratil, J., Maurer, F., Stroba, A., Zhang, H., Biondi, R. M. and Engel, M. (2011) 4-Benzimidazolyl-3-phenylbutanoic acids as novel PIF-pocket-targeting allosteric inhibitors of protein kinase PKCζ. J. Med. Chem. 54, 6714-6723
36. Erdogan, E., Lamark, T., Stallings-Mann, M., Lee, J., Pellecchia, M., Thompson, E. A., Johansen, T. and Fields, A. P. (2006) Aurothiomalate inhibits transformed growth by targeting the PB1 domain of protein kinase Cι. J. Biol. Chem. 281, 28450-28459
37. Collaborative Computational Project-Number 4 (1994) The CCP-4 suite: programs for protein crystallography. Acta Crystallogr., Sect. D: Biol. Crystallogr. 50, 760-763
38. McCoy, A. J., Grosse-Kunstleve, R. W., Adams, P. D., Winn, M. D., Storoni, L. C. and Read, R. J. (2007) Phaser crystallographic software. J. Appl. Crystallogr. 40, 658-674
39. Adams, P. D., Grosse-Kunstleve, R. W., Hung, L. W., Ioerger, T. R., McCoy, A. J., Moriarty, N. W., Read, R. J., Sacchettini, J. C., Sauter, N. K. and Terwilliger, T. C. (2002) PHENIX: building new software for automated crystallographic structure determination. Acta Crystallogr., Sect. D: Biol. Crystallogr. 58, 1948-1954
40. Bain, J., Plater, L., Elliott, M., Shpiro, N., Hastie, C. J., McLauchlan, H., Klevernic, I., Arthur, J. S., Alessi, D. R. and Cohen, P. (2007) The selectivity of protein kinase inhibitors: a further update. Biochem. J. 408, 297-315
41. Romano, R. A., Kannan, N., Kornev, A. P., Allison, C. J. and Taylor, S. S. (2009) A chimeric mechanism for polyvalent trans-phosphorylation of PKA by PDK1. Protein Sci. 18, 1486-1497
42. Leonard, T. A., Rozycki, B., Saidi, L. F., Hummer, G. and Hurley, J. H. (2011) Crystal structure and allosteric activation of protein kinase C βII. Cell 144, 55-66
43. Betschinger, J., Mechtler, K. and Knoblich, J. A. (2003) The Par complex directs asymmetric cell division by phosphorylating the cytoskeletal protein Lgl. Nature 422, 326-330
44. Plant, P. J., Fawcett, J. P., Lin, D. C., Holdorf, A. D., Binns, K., Kulkarni, S. and Pawson, T. (2003) A polarity complex of mPar-6 and atypical PKC binds, phosphorylates and regulates mammalian Lgl. Nat. Cell Biol. 5, 301-308
45. Pears, C. J., Kour, G., House, C., Kemp, B. E. and Parker, P. J. (1990) Mutagenesis of the pseudosubstrate site of protein kinase C leads to activation. Eur. J. Biochem. 194, 89-94
46. Ishiguro, H., Akimoto, K., Nagashima, Y., Kojima, Y., Sasaki, T., Ishiguro-Imagawa, Y., Nakaigawa, N., Ohno, S., Kubota, Y. and Uemura, H. (2009) aPKCλ/ι promotes growth of prostate cancer cells in an autocrine manner through transcriptional activation of interleukin-6. Proc. Natl. Acad. Sci. U.S.A. 106, 16369-16374
47. Horikoshi, Y., Suzuki, A., Yamanaka, T., Sasaki, K., Mizuno, K., Sawada, H., Yonemura, S. and Ohno, S. (2009) Interaction between PAR-3 and the aPKC-PAR-6 complex is indispensable for apical domain development of epithelial cells. J. Cell Sci. 122, 1595-1606
48. Pillai, P., Desai, S., Patel, R., Sajan, M., Farese, R., Ostrov, D. and Acevedo-Duncan, M. (2011) A novel PKC-ι inhibitor abrogates cell proliferation and induces apoptosis in neuroblastoma. Int. J. Biochem. Cell Biol. 43, 784-794
49. Eder, A. M., Sui, X., Rosen, D. G., Nolden, L. K., Cheng, K. W., Lahad, J. P., Kango-Singh, M., Lu, K. H., Warneke, C. L., Atkinson, E. N. et al. (2005) Atypical PKCι contributes to poor prognosis through loss of apical-basal polarity and cyclin E overexpression in ovarian cancer. Proc. Natl. Acad. Sci. U.S.A. 102, 12519-12524
50. Zhang, L., Huang, J., Yang, N., Liang, S., Barchetti, A., Giannakakis, A., Cadungog, M. G., O'Brien-Jenkins, A., Massobrio, M., Roby, K. F. et al. (2006) Integrative genomic analysis of protein kinase C (PKC) family identifies PKCι as a biomarker and potential oncogene in ovarian carcinoma. Cancer Res. 66, 4627-4635
51. Laskowski, R. A. and Swindells, M. B. (2011) LigPlot+: multiple ligand-protein interaction diagrams for drug discovery. J. Chem. Inf. Model. 51, 2778-2786