Identification of the activator-binding residues in the second cysteine-rich regulatory domain of protein kinase Cθ (PKCθ)

Biochemical Journal

Volumn 451, Issue 1, 2013, Pages 33-44

  Rahman, Ghazi M ^a   Shanker, Sreejesh ^b   Lewin, Nancy E ^c   Kedei, Noemi ^c   Hill, Colin S ^c   Prasad, B V Venkataram ^b   Blumberg, Peter M ^c   Das, Joydip ^a  

^a UNIVERSITY OF HOUSTON   (United States)

^b BAYLOR COLLEGE OF MEDICINE   (United States)

^c NATIONAL CANCER INSTITUTE   (United States)

Author keywords

Activator binding residues; Crystal structure; Diacylglycerol; Membrane translocation; Phorbol ester; Phospholipid; Protein kinase C; Tryptophan

Indexed keywords

CYSTEINE; GLYCEROL; PHORBOL ESTER; PHOSPHOLIPID; PROTEIN KINASE C; TRYPTOPHAN;

ARTICLE; BINDING AFFINITY; CELL MEMBRANE; CRYSTAL STRUCTURE; HUMAN; HUMAN CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DOMAIN; PROTEIN STRUCTURE; WILD TYPE;

AMINO ACID SUBSTITUTION; ANIMALS; BINDING SITES; ENZYME ACTIVATORS; ISOENZYMES; MICE; MUTATION, MISSENSE; PROTEIN KINASE C; PROTEIN STRUCTURE, TERTIARY; PROTEIN TRANSPORT; TRYPTOPHAN;

EID: 84875124735     PISSN: 02646021     EISSN: 14708728     Source Type: Journal    
DOI: 10.1042/BJ20121307     Document Type: Article

References (71)

1. Mellor, H. and Parker, P. J. (1998) The extended protein kinase C superfamily. Biochem. J. 332, 281-292
2. Baier, G., Telford, D., Giampa, L., Coggeshall, K. M., Baier-Bitterlich, G., Isakov, N. and Altman, A. (1993) Molecular cloning and characterization of PKCθ, a novel member of the protein kinase C (PKC) gene family expressed predominantly in hematopoietic cells. J. Biol. Chem. 268, 4997-5004
3. Arendt, C. W., Albrecht, B., Soos, T. J. and Littman, D. R. (2002) Protein kinase C-θ: signaling from the center of the T-cell synapse. Curr. Opin. Immunol. 14, 323-330
4. Isakov, N. and Altman, A. (2002) Protein kinase Cθ in T cell activation. Annu. Rev. Immunol. 20, 761-794
5. Healy, A. M., Izmailova, E., Fitzgerald, M., Walker, R., Hattersley, M., Silva, M., Siebert, E., Terkelsen, J., Picarella, D., Pickard, M. D. et al. (2006) PKC-θ-deficient mice are protected from Th1-dependent antigen-induced arthritis. J. Immunol. 177, 1886-1893
6. Salek-Ardakani, S., So, T., Halteman, B. S., Altman, A. and Croft, M. (2004) Differential regulation of Th2 and Th1 lung inflammatory responses by protein kinase C θ. J. Immunol. 173, 6440-6447
7. Salek-Ardakani, S., So, T., Halteman, B. S., Altman, A. and Croft, M. (2005) Protein kinase Cθ controls Th1 cells in experimental autoimmune encephalomyelitis. J. Immunol. 175, 7635-7641
8. Manning, G., Whyte, D. B., Martinez, R., Hunter, T. and Sudarsanam, S. (2002) The protein kinase complement of the human genome. Science 298, 1912-1934
9. Cooke, D. W. and Plotnick, L. (2008) Type 1 diabetes mellitus in pediatrics. Pediatr. Rev. 29, 374-384
10. Marsland, B. J., Soos, T. J., Spath, G., Littman, D. R. and Kopf, M. (2004) Protein kinase C θ is critical for the development of in vivo T helper (Th)2 cell but not Th1 cell responses. J. Exp. Med. 200, 181-189
11. Giannoni, F., Lyon, A. B., Wareing, M. D., Dias, P. B. and Sarawar, S. R. (2005) Protein kinase C θ is not essential for T-cell-mediated clearance of murine gammaherpesvirus 68. J. Virol. 79, 6808-6813
12. Nishizuka, Y. (1992) Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science 258, 607-614
13. Altman, A., Isakov, N. and Baier, G. (2000) Protein kinase Cθ: a new essential superstar on the T-cell stage. Immunol. Today 21, 567-573
14. Nishizuka, Y. (1995) Protein kinase C and lipid signaling for sustained cellular responses. FASEB J. 9, 484-496
15. Irie, K., Oie, K., Nakahara, A., Yanai, Y., Ohigashi, H., Wender, P. A., Fukuda, H., Konishi, H. and Kikkawa, U. (1998) Molecular basis for protein kinase C isozyme-selective binding: the systhesis, folding, and phorbol ester binding of the cysteine-rich domains of all protein kinase C isozymes. J. Am. Chem. Soc. 120, 9159-9167
16. Newton, A. C. (2001) Protein kinase C: structural and spatial regulation by phosphorylation, cofactors, and macromolecular interactions. Chem. Rev. 101, 2353-2364
17. Downward, J., Graves, J. D., Warne, P. H., Rayter, S. and Cantrell, D. A. (1990) Stimulation of p21ras upon T-cell activation. Nature 346, 719-723
18. Chaudhary, D. and Kasaian, M. (2006) PKCθ: a potential therapeutic target for T-cell-mediated diseases. Curr. Opin. Investig. Drugs 7, 432-437
19. Blumberg, P. M., Kedei, N., Lewin, N. E., Yang, D., Czifra, G., Pu, Y., Peach, M. L. and Marquez, V. E. (2008) Wealth of opportunity - the C1 domain as a target for drug development. Curr. Drug Targets 9, 641-652
20. Irie, K., Nakahara, A., Nakagawa, Y., Ohigashi, H., Shindo, M., Fukuda, H., Konishi, H., Kikkawa, U., Kashiwagi, K. and Saito, N. (2002) Establishment of a binding assay for protein kinase C isozymes using synthetic C1 peptides and development of new medicinal leads with protein kinase C isozyme and C1 domain selectivity. Pharmacol. Ther. 93, 271-281
21. Melowic, H. R., Stahelin, R. V., Blatner, N. R., Tian, W., Hayashi, K., Altman, A. and Cho, W. (2007) Mechanism of diacylglycerol-induced membrane targeting and activation of protein kinase Cθ. J. Biol. Chem. 282, 21467-21476
22. Zhang, G., Kazanietz, M. G., Blumberg, P. M. and Hurley, J. H. (1995) Crystal structure of the cys2 activator-binding domain of protein kinase Cδ in complex with phorbol ester. Cell 81, 917-924
23. Kaelin, Jr., W. G., Krek, W., Sellers, W. R., DeCaprio, J. A., Ajchenbaum, F., Fuchs, C. S., Chittenden, T., Li, Y., Farnham, P. J., Blanar, M. A. et al. (1992) Expression cloning of a cDNA encoding a retinoblastoma-binding protein with E2F-like properties. Cell 70, 351-364
24. Charoenthongtrakul, S., Zhou, Q., Shembade, N., Harhaj, N. S. and Harhaj, E. W. (2011) Human T cell leukemia virus type 1 Tax inhibits innate antiviral signaling via NF-κB-dependent induction of SOCS1. J. Virol. 85, 6955-6962
25. Kunkel, T. A. (1985) Rapid and efficient site-specific mutagenesis without phenotypic selection. Proc. Natl. Acad. Sci. U.S.A. 82, 488-492
26. Sugimoto, M., Esaki, N., Tanaka, H. and Soda, K. (1989) A simple and efficient method for the oligonucleotide-directed mutagenesis using plasmid DNA template and phosphorothioate-modified nucleotide. Anal. Biochem. 179, 309-311
27. Nelson, M. and McClelland, M. (1992) Use of DNA methyltransferase/ endonuclease enzyme combinations for megabase mapping of chromosomes. Methods Enzymol. 216, 279-303
28. Stahelin, R. V., Digman, M. A., Medkova, M., Ananthanarayanan, B., Rafter, J. D., Melowic, H. R. and Cho, W. (2004) Mechanism of diacylglycerol-induced membrane targeting and activation of protein kinase Cδ. J. Biol. Chem. 279, 29501-29512
29. Stahelin, R. V., Digman, M. A., Medkova, M., Ananthanarayanan, B., Melowic, H. R., Rafter, J. D. and Cho, W. (2005) Diacylglycerol-induced membrane targeting and activation of protein kinase Cε: mechanistic differences between protein kinases Cδ and Cε. J. Biol. Chem. 280, 19784-19793
30. Quest, A. F., Bardes, E. S., Xie, W. Q., Willott, E., Borchardt, R. A. and Bell, R. M. (1995) Expression of protein kinase Cγ regulatory domain elements containing cysteine-rich zinc-coordinating regions as glutathione S-transferase fusion proteins. Methods Enzymol. 252, 153-167
31. Das, J., Pany, S., Rahman, G. M. and Slater, S. J. (2009) PKCε has an alcohol-binding site in its second cysteine-rich regulatory domain. Biochem. J. 421, 405-413
32. 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
33. Littler, D. R., Walker, J. R., She, Y. M., Finerty, Jr, P. J., Newman, E. M. and Dhe-Paganon, S. (2006) Structure of human protein kinase C η (PKCη) C2 domain and identification of phosphorylation sites. Biochem. Biophys. Res. Commun. 349, 1182-1189
34. Collaborative Computational Project, Number 4 (1994) The CCP4 suite: programs for protein crystallography. Acta Crystallogr. Sect. D Biol. Crystallogr. 50, 760-763
35. Evans, P. (2006) Scaling and assessment of data quality. Acta Crystallogr. Sect. D Biol. Crystallogr. 62, 72-82
36. 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
37. Langer, G., Cohen, S. X., Lamzin, V. S. and Perrakis, A. (2008) Automated macromolecular model building for X-ray crystallography using ARP/wARP version 7. Nat. Protoc. 3, 1171-1179
38. Winn, M. D., Murshudov, G. N. and Papiz, M. Z. (2003) Macromolecular TLS refinement in REFMAC at moderate resolutions. Methods Enzymol. 374, 300-321
39. Emsley, P. and Cowtan, K. (2004) Coot: model-building tools for molecular graphics. Acta Crystallogr. Sect. D Biol. Crystallogr. 60, 2126-2132
40. Dundas, J., Ouyang, Z., Tseng, J., Binkowski, A., Turpaz, Y. and Liang, J. (2006) CASTp: computed atlas of surface topography of proteins with structural and topographical mapping of functionally annotated residues. Nucleic Acids Res. 34, W116-W118
41. Lewin, N. E. and Blumberg, P. M. (2003) [3H]Phorbol 12,13-dibutyrate binding assay for protein kinase C and related proteins. Methods Mol. Biol. 233, 129-156
42. Das, J., Pany, S. and Majhi, A. (2011) Chemical modifications of resveratrol for improved protein kinase Cα activity. Bioorg. Med. Chem. 19, 5321-5333
43. Chen, N., Ma, W., Huang, C. and Dong, Z. (1999) Translocation of protein kinase Cε and protein kinase Cδ to membrane is required for ultraviolet B-induced activation of mitogen-activated protein kinases and apoptosis. J. Biol. Chem. 274, 15389-15394
44. Slater, S. J., Kelly, M. B., Taddeo, F. J., Rubin, E. and Stubbs, C. D. (1994) Evidence for discrete diacylglycerol and phorbol ester activator sites on protein kinase C. Differences in effects of 1-alkanol inhibition, activation by phosphatidylethanolamine and calcium chelation. J. Biol. Chem. 269, 17160-17165
45. Geczy, T., Peach, M. L., El Kazzouli, S., Sigano, D. M., Kang, J. H., Valle, C. J., Selezneva, J., Woo, W., Kedei, N., Lewin, N. E. et al. (2012) Molecular basis for the failure of the "atypical" C1 domain of Vav1 to bind diacylglycerol/phorbol ester. J. Biol. Chem. 287, 13137-13158
46. Shanmugasundararaj, S., Das, J., Sandberg, W. S., Zhou, X., Wang, D., Messing, R. O., Bruzik, K. S., Stehle, T. and Miller, K. W. (2012) Structural and functional characterization of an anesthetic binding site in the second cysteine-rich domain of protein kinase Cδ. Biophys. J. 103, 2331-2340
47. Kazanietz, M. G., Wang, S., Milne, G. W., Lewin, N. E., Liu, H. L. and Blumberg, P. M. (1995) Residues in the second cysteine-rich region of protein kinase Cδ relevant to phorbol ester binding as revealed by site-directed mutagenesis. J. Biol. Chem. 270, 21852-21859
48. Schultz, A., Ling, M. and Larsson, C. (2004) Identification of an amino acid residue in the protein kinase C C1b domain crucial for its localization to the Golgi network. J. Biol. Chem. 279, 31750-31760
49. Kashiwagi, K., Shirai, Y., Kuriyama, M., Sakai, N. and Saito, N. (2002) Importance of C1B domain for lipid messenger-induced targeting of protein kinase C. J. Biol. Chem. 277, 18037-18045
50. Lopez-Nicolas, R., Lopez-Andreo, M. J., Marin-Vicente, C., Gomez-Fernandez, J. C. and Corbalan-Garcia, S. (2006) Molecular mechanisms of PKCα localization and activation by arachidonic acid. The C2 domain also plays a role. J. Mol. Biol. 357, 1105-1120
51. Pak, Y., Enyedy, I. J., Varady, J., Kung, J. W., Lorenzo, P. S., Blumberg, P. M. and Wang, S. (2001) Structural basis of binding of high-affinity ligands to protein kinase C: prediction of the binding modes through a new molecular dynamics method and evaluation by site-directed mutagenesis. J. Med. Chem. 44, 1690-1701
52. Dries, D. R., Gallegos, L. L. and Newton, A. C. (2007) A single residue in the C1 domain sensitizes novel protein kinase C isoforms to cellular diacylglycerol production. J. Biol. Chem. 282, 826-830
53. Carrasco, S. and Merida, I. (2004) Diacylglycerol-dependent binding recruits PKCθ and RasGRP1 C1 domains to specific subcellular localizations in living T lymphocytes. Mol. Biol. Cell. 15, 2932-2942
54. Wang, Q. J., Fang, T. W., Nacro, K., Marquez, V. E., Wang, S. and Blumberg, P. M. (2001) Role of hydrophobic residues in the C1b domain of protein kinase Cδ on ligand and phospholipid interactions. J. Biol. Chem. 276, 19580-19587
55. Monks, C. R., Kupfer, H., Tamir, I., Barlow, A. and Kupfer, A. (1997) Selective modulation of protein kinase C-θ during T-cell activation. Nature 385, 83-86
56. Grakoui, A., Bromley, S. K., Sumen, C., Davis, M. M., Shaw, A. S., Allen, P. M. and Dustin, M. L. (1999) The immunological synapse: a molecular machine controlling T cell activation. Science 285, 221-227
57. Bazzi, M. D. and Nelsestuen, G. L. (1988) Properties of membrane-inserted protein kinase C. Biochemistry 27, 7589-7593
58. Kazanietz, M. G., Krausz, K. W. and Blumberg, P. M. (1992) Differential irreversible insertion of protein kinase C into phospholipid vesicles by phorbol esters and related activators. J. Biol. Chem. 267, 20878-20886
59. Ananthanarayanan, B., Stahelin, R. V., Digman, M. A. and Cho, W. (2003) Activation mechanisms of conventional protein kinase C isoforms are determined by the ligand affinity and conformational flexibility of their C1 domains. J. Biol. Chem. 278, 46886-46894
60. Stewart, M. D., Morgan, B., Massi, F. and Igumenova, T. I. (2011) Probing the determinants of diacylglycerol binding affinity in the C1B domain of protein kinase Cα. J. Mol. Biol. 408, 949-970
61. McGaughey, G. B., Gagne, M. and Rappe, A. K. (1998) π-Stacking interactions. Alive and well in proteins. J. Biol. Chem. 273, 15458-15463
62. Wang, L., Sun, N., Terzyan, S., Zhang, X. and Benson, D. R. (2006) A histidine/tryptophan π-stacking interaction stabilizes the heme-independent folding core of microsomal apocytochrome b5 relative to that of mitochondrial apocytochrome b5. Biochemistry 45, 13750-13759
63. Dougherty, D. A. (1996) Cation-π interactions in chemistry and biology: a new view of benzene, Phe, Tyr, and Trp. Science 271, 163-168
64. Gallivan, J. P. and Dougherty, D. A. (1999) Cation-π interactions in structural biology. Proc. Natl. Acad. Sci. U.S.A. 96, 9459-9464
65. Takeuchi, H., Okada, A. and Miura, T. (2003) Roles of the histidine and tryptophan side chains in the M2 proton channel from influenza A virus. FEBS Lett. 552, 35-38
66. Shen, N., Guryev, O. and Rizo, J. (2005) Intramolecular occlusion of the diacylglycerol-binding site in the C1 domain of munc13-1. Biochemistry 44, 1089-1096
67. Canagarajah, B., Leskow, F. C., Ho, J. Y., Mischak, H., Saidi, L. F., Kazanietz, M. G. and Hurley, J. H. (2004) Structural mechanism for lipid activation of the Rac-specific GAP, β2-chimaerin. Cell 119, 407-418
68. Giorgione, J. R., Lin, J. H., McCammon, J. A. and Newton, A. C. (2006) Increased membrane affinity of the C1 domain of protein kinase Cδ compensates for the lack of involvement of its C2 domain in membrane recruitment. J. Biol. Chem. 281, 1660-1669
69. Slater, S. J., Seiz, J. L., Cook, A. C., Buzas, C. J., Malinowski, S. A., Kershner, J. L., Stagliano, B. A. and Stubbs, C. D. (2002) Regulation of PKCα activity by C1-C2 domain interactions. J. Biol. Chem. 277, 15277-15285
70. Stahelin, R. V., Wang, J., Blatner, N. R., Rafter, J. D., Murray, D. and Cho, W. (2005) The origin of C1A-C2 interdomain interactions in protein kinase Cα. J. Biol. Chem. 280, 36452-36463
71. Pu, Y., Peach, M. L., Garfield, S. H., Wincovitch, S., Marquez, V. E. and Blumberg, P. M. (2006) Effects on ligand interaction and membrane translocation of the positively charged arginine residues situated along the C1 domain binding cleft in the atypical protein kinase C isoforms. J. Biol. Chem. 281, 33773-33788