Dynamics and Membrane Interactions of Protein Kinase C

Biochemistry

Volumn 54, Issue 32, 2015, Pages 4953-4968

  Igumenova, Tatyana I ^a  

^a TEXAS A AND M UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BIOCHEMISTRY; CHEMISTRY;

CELLULAR PROCESS; MEMBRANE INTERACTIONS; MULTIDOMAIN STRUCTURE; PHORBOL ESTERS; PHOSPHOINOSITIDE SIGNALING PATHWAYS; PROTEIN KINASE C; RESEARCH EFFORTS; STRUCTURAL BIOLOGY;

ENZYMES;

PROTEIN KINASE C; ISOENZYME;

ARTICLE; BIOPHYSICS; ENZYME ACTIVITY; ENZYME PHOSPHORYLATION; ENZYME STRUCTURE; MEMBRANE; NONHUMAN; PRIORITY JOURNAL; PROTEIN INTERACTION; RAT; AMINO ACID SEQUENCE; ANIMAL; BIOLOGICAL MODEL; CHEMICAL STRUCTURE; CHEMISTRY; ENZYME ACTIVATION; GENETICS; HUMAN; METABOLISM; MOLECULAR DYNAMICS; MOLECULAR GENETICS; PROTEIN MULTIMERIZATION; PROTEIN TERTIARY STRUCTURE; SEQUENCE HOMOLOGY; SIGNAL TRANSDUCTION;

AMINO ACID SEQUENCE; ANIMALS; BIOPHYSICAL PHENOMENA; ENZYME ACTIVATION; HUMANS; ISOENZYMES; MODELS, BIOLOGICAL; MODELS, MOLECULAR; MOLECULAR DYNAMICS SIMULATION; MOLECULAR SEQUENCE DATA; PROTEIN KINASE C; PROTEIN MULTIMERIZATION; PROTEIN STRUCTURE, TERTIARY; SEQUENCE HOMOLOGY, AMINO ACID; SIGNAL TRANSDUCTION;

EID: 84939783634     PISSN: 00062960     EISSN: 15204995     Source Type: Journal    
DOI: 10.1021/acs.biochem.5b00565     Document Type: Article

References (140)

1. Inoue, M., Kishimoto, A., Takai, Y., and Nishizuka, Y. (1977) Studies on a cyclic nucleotide-independent protein kinase and its proenzyme in mammalian tissues. 2. Proenzyme and its actiavtion by calcium-dependent protease from rat brain J. Biol. Chem. 252, 7610-7616
2. Takai, Y., Kishimoto, A., Inoue, M., and Nishizuka, Y. (1977) Studies on a cyclic nucleotide-independent protein kinase and its proenzyme in mammalian tissues. 1. Purification and characterization of an active enzyme from bovine cerebellum J. Biol. Chem. 252, 7603-7609
3. Castagna, M., Takai, Y., Kaibuchi, K., Sano, K., Kikkawa, U., and Nishizuka, Y. (1982) Direct Activation of Calcium-Activated, Phospholipid-Dependent Protein-Kinase by Tumor-Promoting Phorbol Esters J. Biol. Chem. 257, 7847-7851
4. Newton, A. C. (2001) Protein kinase C: Structural and spatial regulation by phosphorylation, cofactors, and macromolecular interactions Chem. Rev. 101, 2353-2364 10.1021/cr0002801
5. Rosse, C., Linch, M., Kermorgant, S., Cameron, A. J. M., Boeckeler, K., and Parker, P. J. (2010) PKC and the control of localized signal dynamics Nat. Rev. Mol. Cell Biol. 11, 103-112 10.1038/nrm2847
6. Steinberg, S. F. (2008) Structural basis of protein kinase C isoform function Physiol. Rev. 88, 1341-1378 10.1152/physrev.00034.2007
7. Moscat, J. and Diaz-Meco, M. T. (2000) The atypical protein kinase Cs-Functional specificity mediated by specific protein adapters EMBO Rep. 1, 399-403 10.1093/embo-reports/kvd098
8. Suzuki, A., Akimoto, K., and Ohno, S. (2003) Protein kinase C lambda/iota (PKC lambda/iota): A PKC isotype essential for the development of multicellular organisms J. Biochem. 133, 9-16 10.1093/jb/mvg018
9. Abrial, E., Lucas, G., Scarna, H., Haddjeri, N., and Lambas-Senas, L. (2011) A role for the PKC signaling system in the pathophysiology and treatment of mood disorders: involvement of a functional imbalance? Mol. Neurobiol. 44, 407-419 10.1007/s12035-011-8210-4
10. Churchill, E., Budas, G., Vallentin, A., Koyanagi, T., and Mochly-Rosen, D. (2008) PKC Isozymes in chronic cardiac disease: Possible therapeutic targets? Annu. Rev. Pharmacol. Toxicol. 48, 569-599 10.1146/annurev.pharmtox.48.121806.154902
11. Griner, E. M. and Kazanietz, M. G. (2007) Protein kinase C and other diacylglycerol effectors in cancer Nat. Rev. Cancer 7, 281-294 10.1038/nrc2110
12. Geraldes, P. and King, G. L. (2010) Activation of protein kinase C isoforms and its impact on diabetic complications Circ. Res. 106, 1319-1331 10.1161/CIRCRESAHA.110.217117
13. Pass, J. M., Gao, J. M., Jones, W. K., Wead, W. B., Wu, X., Zhang, J., Baines, C. P., Bolli, R., Zheng, Y. T., Joshua, I. G., and Ping, P. P. (2001) Enhanced PKC beta II translocation and PKC beta II-RACK1 interactions in PKC epsilon-induced heart failure: a role for RACK1 American Journal of Physiology-Heart and Circulatory Physiology 281, H2500-H2510
14. Ping, P. P., Zhang, J., Qiu, Y. M., Tang, X. L., Manchikalapudi, S., Cao, X. N., and Bolli, R. (1997) Ischemic preconditioning induces selective translocation of protein kinase C isoforms epsilon and eta in the heart of conscious rabbits without subcellular redistribution of total protein kinase C activity Circ. Res. 81, 404-414 10.1161/01.RES.81.3.404
15. Hambleton, M., Hahn, H., Pleger, S. T., Kuhn, M. C., Klevitsky, R., Carr, A. N., Kimball, T. F., Hewett, T. E., Ii, G. W., Koch, W. J., and Molkentin, J. D. (2006) Pharmacological- and gene therapy-based inhibition of protein kinase C alpha/beta enhances cardiac contractility and attenuates heart failure Circulation 114, 574-582 10.1161/CIRCULATIONAHA.105.592550
16. Braz, J. C., Gregory, K., Pathak, A., Zhao, W., Sahin, B., Klevitsky, R., Kimball, T. F., Lorenz, J. N., Nairn, A. C., Liggett, S. B., Bodi, I., Wang, S., Schwartz, A., Lakatta, E. G., DePaoli-Roach, A. A., Robbins, J., Hewett, T. E., Bibb, J. A., Westfall, M. V., Kranias, E. G., and Molkentin, J. D. (2004) PKC-alpha regulates cardiac contractility and propensity toward heart failure Nat. Med. 10, 248-254 10.1038/nm1000
17. Gilio, K., Harper, M. T., Cosemans, J., Konopatskaya, O., Munnix, I. C. A., Prinzen, L., Leitges, M., Liu, Q. H., Molkentin, J. D., Heemskerk, J. W. M., and Poole, A. W. (2010) Functional Divergence of Platelet Protein Kinase C (PKC) Isoforms in Thrombus Formation on Collagen J. Biol. Chem. 285, 23410-23419 10.1074/jbc.M110.136176
18. Konopatskaya, O., Gilio, K., Harper, M. T., Zhao, Y., Cosemans, J., Karim, Z. A., Whiteheart, S. W., Molkentin, J. D., Verkade, P., Watson, S. P., Heemskerk, J. W. M., and Poole, A. W. (2009) PKC alpha regulates platelet granule secretion and thrombus formation in mice J. Clin. Invest. 119, 399-407 10.1172/JCI34665
19. Yoshioka, A., Shirakawa, R., Nishioka, H., Tabuchi, A., Higashi, T., Ozaki, H., Yamamoto, A., Kita, T., and Horiuchi, H. (2001) Identification of protein kinase C alpha as an essential, but not sufficient, cytosolic factor for Ca2+-induced alpha- and dense-core granule secretion in platelets J. Biol. Chem. 276, 39379-39385 10.1074/jbc.M102933200
20. Li, Q., Subbulakshmi, V., Fields, A. P., Murray, N. R., and Cathcart, M. K. (1999) Protein kinase calpha regulates human monocyte O-2 production and low density lipoprotein lipid oxidation J. Biol. Chem. 274, 3764-3771 10.1074/jbc.274.6.3764
21. Marino, M., Distefano, E., Pallottini, V., Caporali, S., Bruscalupi, G., and Trentalance, A. (2001) Activation of IP(3)-protein kinase C-alpha signal transduction pathway precedes the changes of plasma cholesterol, hepatic lipid metabolism and induction of low-density lipoprotein receptor expression in 17-beta-oestradiol-treated rats Exp. Physiol. 86, 39-45 10.1113/eph8602069
22. Kim, J., Thorne, S. H., Sun, L., Huang, B., and Mochly-Rosen, D. (2011) Sustained inhibition of PKCalpha reduces intravasation and lung seeding during mammary tumor metastasis in an in vivo mouse model Oncogene 30, 323-333 10.1038/onc.2010.415
23. Lønne, G. K., Cornmark, L., Zahirovic, I. O., Landberg, G., Jirstrom, K., and Larsson, C. (2010) PKCalpha expression is a marker for breast cancer aggressiveness Mol. Cancer 9, 76 10.1186/1476-4598-9-76
24. Smith, S. D., Enge, M., Bao, W., Thullberg, M., Costa, T. D., Olofsson, H., Gashi, B., Selivanova, G., and Stromblad, S. (2012) Protein Kinase Calpha (PKCalpha) Regulates p53 Localization and Melanoma Cell Survival Downstream of Integrin alphav in Three-dimensional Collagen and in Vivo J. Biol. Chem. 287, 29336-29347 10.1074/jbc.M112.341917
25. Varga, A., Czifra, G., Tallai, B., Nemeth, T., Kovacs, I., Kovacs, L., and Bíró, T. (2004) Tumor grade-dependent alterations in the protein kinase C isoform pattern in urinary bladder carcinomas Eur. Urol. 46, 462-465 10.1016/j.eururo.2004.04.014
26. Mandil, R., Ashkenazi, E., Blass, M., Kronfeld, I., Kazimirsky, G., Rosenthal, G., Umansky, F., Lorenzo, P. S., Blumberg, P. M., and Brodie, C. (2001) Protein kinase Calpha and protein kinase Cdelta play opposite roles in the proliferation and apoptosis of glioma cells Cancer Res. 61, 4612-4619
27. Chen, L., Hahn, H., Wu, G. Y., Chen, C. H., Liron, T., Schechtman, D., Cavallaro, G., Banci, L., Guo, Y. R., Bolli, R., Dorn, G. W., and Mochly-Rosen, D. (2001) Opposing cardioprotective actions and parallel hypertrophic effects of delta PKC and epsilon PKC Proc. Natl. Acad. Sci. U. S. A. 98, 11114-11119 10.1073/pnas.191369098
28. Dorn, G. W., Souroujon, M. C., Liron, T., Chen, C. H., Gray, M. O., Zhou, H. Z., Csukai, M., Wu, G. Y., Lorenz, J. N., and Mochly-Rosen, D. (1999) Sustained in vivo cardiac protection by a rationally designed peptide that causes epsilon protein kinase C translocation Proc. Natl. Acad. Sci. U. S. A. 96, 12798-12803 10.1073/pnas.96.22.12798
29. Hahn, H. S., Yussman, M. G., Toyokawa, T., Marreez, Y., Barrett, T. J., Hilty, K. C., Osinska, H., Robbins, J., and Dorn, G. W. (2002) Ischemic protection and myofibrillar cardiomyopathy-Dose-dependent effects of in vivo delta PKC inhibition Circ. Res. 91, 741-748 10.1161/01.RES.0000037091.64492.69
30. Inagaki, K., Chen, L., Ikeno, F., Lee, F. H., Imahashi, K., Bouley, D. M., Rezaee, M., Yock, P. G., Murphy, E., and Mochly-Rosen, D. (2003) Inhibition of delta-protein kinase C protects against reperfusion injury of the ischemic heart in vivo Circulation 108, 2304-2307 10.1161/01.CIR.0000101682.24138.36
31. Inagaki, K., Begley, R., Ikeno, F., and Mochly-Rosen, D. (2005) Cardioprotection by epsilon-protein kinase C activation from ischemia-Continuous delivery and antiarrhythmic effect of an epsilon-protein kinase C-activating peptide Circulation 111, 44-50 10.1161/01.CIR.0000151614.22282.F1
32. Ping, P. P., Song, C. X., Zhang, J., Guo, Y. R., Cao, X. N., Li, R. C. X., Wu, W. J., Vondriska, T. M., Pass, J. M., Tang, X. L., Pierce, W. M., and Bolli, R. (2002) Formation of protein kinase C epsilon-Lck signalling modules confers cardioprotection J. Clin. Invest. 109, 499-507 10.1172/JCI0213200
33. Saurin, A. T., Pennington, D. J., Raat, N. J. H., Latchman, D. S., Owen, M. J., and Marber, M. S. (2002) Targeted disruption of the protein kinase C epsilon gene abolishes the infarct size reduction that follows ischaemic preconditioning of isolated buffer-perfused mouse hearts Cardiovasc. Res. 55, 672-680 10.1016/S0008-6363(02)00325-5
34. House, C. and Kemp, B. E. (1987) Protein-Kinase-C Contains a Pseudosubstrate Prototype in Its Regulatory Domain Science 238, 1726-1728 10.1126/science.3686012
35. Nishikawa, K., Toker, A., Johannes, F. J., Zhou, S. Y., and Cantley, L. C. (1997) Determination of the specific substrate sequence motifs of protein kinase C isozymes J. Biol. Chem. 272, 952-960 10.1074/jbc.272.2.952
36. Orr, J. W. and Newton, A. C. (1994) Intrapeptide Regulation of Protein-Kinase-C J. Biol. Chem. 269, 8383-8387
37. 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 10.1111/j.1432-1033.1990.tb19431.x
38. Ron, D. and Mochlyrosen, D. (1995) An autoregulatory region in protein kinase C-the pseudoanchoring site Proc. Natl. Acad. Sci. U. S. A. 92, 492-496 10.1073/pnas.92.2.492
39. Leonard, T. A., Rozycki, B., Saidi, L. F., Hummer, G., and Hurley, J. H. (2011) Crystal structure and allosteric activation of protein kinase C betaII Cell 144, 55-66 10.1016/j.cell.2010.12.013
40. Stahelin, R. V., Wang, J. Y., Blatner, N. R., Raftner, J. D., Murray, D., and Cho, W. H. (2005) The origin of C1A-C2 interdomain interactions in protein kinase C alpha J. Biol. Chem. 280, 36452-36463 10.1074/jbc.M506224200
41. 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 PKC alpha activity by C1-C2 domain interactions J. Biol. Chem. 277, 15277-15285 10.1074/jbc.M112207200
42. Stensman, H. and Larsson, C. (2007) Identification of acidic amino acid residues in the protein kinase C alpha V5 domain that contribute to its insensitivity to diacylglycerol J. Biol. Chem. 282, 28627-28638 10.1074/jbc.M702248200
43. Edwards, A. S. and Newton, A. C. (1997) Phosphorylation at conserved carboxyl-terminal hydrophobic motif regulates the catalytic and regulatory domains of protein kinase C J. Biol. Chem. 272, 18382-18390 10.1074/jbc.272.29.18382
44. Kheifets, V. and Mochly-Rosen, D. (2007) Insight into intra- and inter-molecular interactions of PKC: design of specific modulators of kinase function Pharmacol. Res. 55, 467-476 10.1016/j.phrs.2007.04.014
45. Solodukhin, A. S., Kretsinger, R. H., and Sando, J. J. (2007) Initial three-dimensional reconstructions of protein kinase C delta from two-dimensional crystals on lipid monolayers Cell. Signalling 19, 2035-2045 10.1016/j.cellsig.2007.05.010
46. Huang, S. M., Leventhal, P. S., Wiepz, G. J., and Bertics, P. J. (1999) Calcium and phosphatidylserine stimulate the self-association of conventional protein kinase C isoforms Biochemistry 38, 12020-12027 10.1021/bi990594m
47. Swanson, C. J., Ritt, M., Wang, W., Lang, M. J., Narayan, A., Tesmer, J. J., Westfall, M., and Sivaramakrishnan, S. (2014) Conserved Modular Domains Team up to Latch-open Active Protein Kinase C alpha J. Biol. Chem. 289, 17812-17829 10.1074/jbc.M113.534750
48. Antal, C. E., Violin, J. D., Kunkel, M. T., Skovsø, S., and Newton, A. C. (2014) Intramolecular Conformational Changes Optimize Protein Kinase C Signaling Chem. Biol. 21, 459-469 10.1016/j.chembiol.2014.02.008
49. Ziemba, B. P., Li, J. N., Landgraf, K. E., Knight, J. D., Voth, G. A., and Falke, J. J. (2014) Single-Molecule Studies Reveal a Hidden Key Step in the Activation Mechanism of Membrane-Bound Protein Kinase C-alpha Biochemistry 53, 1697-1713 10.1021/bi4016082
50. Medkova, M. and Cho, W. (1998) Mutagenesis of the C2 domain of protein kinase C-alpha. Differential roles of Ca2+ ligands and membrane binding residues J. Biol. Chem. 273, 17544-17552 10.1074/jbc.273.28.17544
51. Nalefski, E. A. and Newton, A. C. (2001) Membrane binding kinetics of protein kinase C betaII mediated by the C2 domain Biochemistry 40, 13216-13229 10.1021/bi010761u
52. Braun, D. C., Garfield, S. H., and Blumberg, P. M. (2005) Analysis by fluorescence resonance energy transfer of the interaction between ligands and protein kinase C delta in the intact cell J. Biol. Chem. 280, 8164-8171 10.1074/jbc.M413896200
53. 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 10.1074/jbc.C600268200
54. Cho, W. and Stahelin, R. V. (2006) Membrane binding and subcellular targeting of C2 domains Biochim. Biophys. Acta, Mol. Cell Biol. Lipids 1761, 838-849 10.1016/j.bbalip.2006.06.014
55. Shao, X. G., Davletov, B. A., Sutton, R. B., Sudhof, T. C., and Rizo, J. (1996) Bipartite Ca2+-binding motif in C-2 domains of synaptotagmin and protein kinase C Science 273, 248-251 10.1126/science.273.5272.248
56. Benes, C. H., Wu, N., Elia, A. E. H., Dharia, T., Cantley, L. C., and Soltoff, S. P. (2005) The C2 domain of PKC delta is a phosphotyrosine binding domain Cell 121, 271-280 10.1016/j.cell.2005.02.019
57. Stahelin, R. V., Kong, K. F., Raha, S., Tian, W., Melowic, H. R., Ward, K. E., Murray, D., Altman, A., and Cho, W. (2012) Protein Kinase C theta C2 Domain Is a Phosphotyrosine Binding Module That Plays a Key Role in Its Activation J. Biol. Chem. 287, 30518-30528 10.1074/jbc.M112.391557
58. Guerrero-Valero, M., Marin-Vicente, C., Gomez-Fernandez, J. C., and Corbalan-Garcia, S. (2007) The C2 domains of classical PKCs are specific PtdIns(4,5)P-2-sensing domains with different affinities for membrane binding J. Mol. Biol. 371, 608-621 10.1016/j.jmb.2007.05.086
59. Manna, D., Bhardwaj, N., Vora, M. S., Stahelin, R. V., Lu, H., and Cho, W. H. (2008) Differential roles of phosphatidylserine, PtdIns(4,5)P-2, and PtdIns(3,4,5)P-3 in plasma membrane targeting of C2 domains-Molecular dynamics simulation, membrane binding, and cell translocation studies of the PKC alpha C2 domain J. Biol. Chem. 283, 26047-26058 10.1074/jbc.M802617200
60. Guerrero-Valero, M., Ferrer-Orta, C., Querol-Audi, J., Marin-Vicente, C., Fita, I., Gomez-Fernandez, J. C., Verdaguer, N., and Corbalan-Garcia, S. (2009) Structural and mechanistic insights into the association of PKC alpha-C2 domain to PtdIns(4,5)P-2 Proc. Natl. Acad. Sci. U. S. A. 106, 6603-6607 10.1073/pnas.0813099106
61. Morales, K. A., Yang, Y., Long, Z., Li, P., Taylor, A. B., Hart, P. J., and Igumenova, T. I. (2013) Cd2+ as a Ca2+ surrogate in protein-membrane interactions: isostructural but not isofunctional J. Am. Chem. Soc. 135, 12980-12983 10.1021/ja406958k
62. Morales, K. A., Lasagna, M., Gribenko, A. V., Yoon, Y., Reinhart, G. D., Lee, J. C., Cho, W., Li, P., and Igumenova, T. I. (2011) Pb2+ as modulator of protein-membrane interactions J. Am. Chem. Soc. 133, 10599-10611 10.1021/ja2032772
63. Kohout, S. C., Corbalan-Garcia, S., Torrecillas, A., Gomez-Fernandez, J. C., and Falke, J. J. (2002) C2 domains of protein kinase C isoforms alpha, beta, and gamma: Activation parameters and calcium stoichiometries of the membrane-bound state Biochemistry 41, 11411-11424 10.1021/bi026041k
64. Murray, D. and Honig, B. (2002) Electrostatic control of the membrane targeting of C2 domains Mol. Cell 9, 145-154 10.1016/S1097-2765(01)00426-9
65. Markovac, J. and Goldstein, G. W. (1988) Picomolar concentrations of lead stimulate brain protein kinase C Nature 334, 71-73 10.1038/334071a0
66. Sun, X. Y., Tian, X. T., Tomsig, J. L., and Suszkiw, J. B. (1999) Analysis of differential effects of Pb2+ on protein kinase C isozymes Toxicol. Appl. Pharmacol. 156, 40-45 10.1006/taap.1999.8622
67. Edwards, A. S. and Newton, A. C. (1997) Regulation of protein kinase C beta II by its C2 domain Biochemistry 36, 15615-15623 10.1021/bi9718752
68. Torrecillas, A., Laynez, J., Menendez, M., Corbalan-Garcia, S., and Gomez-Fernandez, J. C. (2004) Calorimetric study of the interaction of the C2 domains of classical protein kinase C isoenzymes with Ca2+ and phospholipids Biochemistry 43, 11727-11739 10.1021/bi0489659
69. Verdaguer, N., Corbalan-Garcia, S., Ochoa, W. F., Fita, I., and Gomez-Fernandez, J. C. (1999) Ca2+ bridges the C2 membrane-binding domain of protein kinase C alpha directly to phosphatidylserine EMBO J. 18, 6329-6338 10.1093/emboj/18.22.6329
70. Banci, L., Cavallaro, G., Kheifets, V., and Mochly-Rosen, D. (2002) Molecular dynamics characterization of the C2 domain of protein kinase C beta J. Biol. Chem. 277, 12988-12997 10.1074/jbc.M106875200
71. Stahelin, R. V., Rafter, J. D., Das, S., and Cho, W. (2003) The molecular basis of differential subcellular localization of C2 domains of protein kinase C-alpha and group IVa cytosolic phospholipase A(2) J. Biol. Chem. 278, 12452-12460 10.1074/jbc.M212864200
72. Scott, A. M., Antal, C. E., and Newton, A. C. (2013) Electrostatic and Hydrophobic Interactions Differentially Tune Membrane Binding Kinetics of the C2 Domain of Protein Kinase C alpha J. Biol. Chem. 288, 16905-16915 10.1074/jbc.M113.467456
73. Kohout, S. C., Corbalan-Garcia, S., Gomez-Fernandez, J. C., and Falke, J. J. (2003) C2 domain of protein kinase C alpha: Elucidation of the membrane docking surface by site-directed fluorescence and spin labeling Biochemistry 42, 1254-1265 10.1021/bi026596f
74. Landgraf, K. E., Malmberg, N. J., and Falke, J. J. (2008) Effect of PIP(2) binding on the membrane docking geometry of PKC alpha C2 domain: An EPR site-directed spin-labeling and relaxation study Biochemistry 47, 8301-8316 10.1021/bi800711t
75. Stewart, M. D., Cole, T. R., and Igumenova, T. I. (2014) Interfacial Partitioning of a Loop Hinge Residue Contributes to Diacylglycerol Affinity of Conserved Region 1 Domains J. Biol. Chem. 289, 27653-27664 10.1074/jbc.M114.585570
76. Dancea, F., Kami, K., and Overduin, M. (2008) Lipid interaction networks of peripheral membrane proteins revealed by data-driven micelle docking Biophys. J. 94, 515-524 10.1529/biophysj.107.115923
77. Sanchez-Bautista, S., Marin-Vicente, C., Gomez-Fernandez, J. C., and Corbalan-Garcia, S. (2006) The C2 domain of PKC alpha is a Ca2+-dependent PtdIns(4,5)P-2 sensing domain: A new insight into an old pathway J. Mol. Biol. 362, 901-914 10.1016/j.jmb.2006.07.093
78. Evans, J. H., Murray, D., Leslie, C. C., and Falke, J. J. (2005) Specific translocation of protein kinase C alpha to the plasma membrane requires both Ca2+ and PIP2 recognition by its C2 domain Mol. Biol. Cell 17, 56-66 10.1091/mbc.E05-06-0499
79. Morales, K. A. and Igumenova, T. I. (2012) Synergistic Effect of Pb(2+) and Phosphatidylinositol 4,5-Bisphosphate on C2 Domain-Membrane Interactions Biochemistry 51, 3349 10.1021/bi201850h
80. Corbin, J. A., Evans, J. H., Landgraf, K. E., and Falke, J. J. (2007) Mechanism of specific membrane targeting by C2 domains: Localized pools of target lipids enhance Ca(2+) affinity Biochemistry 46, 4322-4336 10.1021/bi062140c
81. Gallegos, L. L. and Newton, A. C. (2008) Spatiotemporal dynamics of lipid signaling: protein kinase C as a paradigm IUBMB Life 60, 782-789 10.1002/iub.122
82. Hurley, J. H., Newton, A. C., Parker, P. J., Blumberg, P. M., and Nishizuka, Y. (1997) Taxonomy and function of C1 protein kinase C homology domains Protein Sci. 6, 477-480 10.1002/pro.5560060228
83. Xu, R. X., Pawelczyk, T., Xia, T. H., and Brown, S. C. (1997) NMR structure of a protein kinase C-gamma phorbol-binding domain and study of protein-lipid micelle interactions Biochemistry 36, 10709-10717 10.1021/bi970833a
84. Zhang, G. G., Kazanietz, M. G., Blumberg, P. M., and Hurley, J. H. (1995) Crystal-Structure of the Cys2 Activator-Binding Domain of Protein-Kinase C-Delta in Complex with Phorbol Ester Cell 81, 917-924 10.1016/0092-8674(95)90011-X
85. Rahman, G. M., Shanker, S., Lewin, N. E., Kedei, N., Hill, C. S., Prasad, B. V. V, Blumberg, P. M., and Das, J. (2013) Identification of the activator-binding residues in the second cysteine-rich regulatory domain of protein kinase C theta (PKC theta) Biochem. J. 451 (451) 33-44 10.1042/BJ20121307
86. Shanmugasundararaj, S., Das, J., Sandberg, W. S., Zhou, X. J., 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 C delta Biophys. J. 103, 2331-2340 10.1016/j.bpj.2012.10.034
87. Grishin, N. V. (2001) Treble clef finger-a functionally diverse zinc-binding structural motif Nucleic Acids Res. 29, 1703-1714 10.1093/nar/29.8.1703
88. Saraiva, L., Fresco, P., Pinto, E., and Goncalves, J. (2004) Characterization of phorbol esters activity on individual mammalian protein kinase C isoforms, using the yeast phenotypic assay Eur. J. Pharmacol. 491, 101-110 10.1016/j.ejphar.2004.03.035
89. Kimura, K., Mizutani, M. Y., Tomioka, N., Endo, Y., Shudo, K., and Itai, A. (1999) Docking study of bryostatins to protein kinase C delta Cys2 domain Chem. Pharm. Bull. 47, 1134-1137 10.1248/cpb.47.1134
90. Pak, Y., Enyedy, I. J., Varady, J., Kung, J. W., Lorenzo, P. S., Blumberg, P. M., and Wang, S. M. (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 10.1021/jm000488e
91. Li, J. N., Ziemba, B. P., Falke, J. J., and Voth, G. A. (2014) Interactions of Protein Kinase C-alpha C1A and C1B Domains with Membranes: A Combined Computational and Experimental Study J. Am. Chem. Soc. 136, 11757-11766 10.1021/ja505369r
92. 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 10.1016/j.ceb.2009.01.019
93. Goel, G., Makkar, H. P., Francis, G., and Becker, K. (2007) Phorbol esters: structure, biological activity, and toxicity in animals Int. J. Toxicol. 26, 279-288 10.1080/10915810701464641
94. Kazanietz, M. G. and Lorenzo, P. S. (2003) Phorbol esters as probes for the study of protein kinase C function. In Protein Kinase C Protocols (Newton, A. C., Ed.) pp 423-429, Springer, Dordrecht, The Netherlands.
95. Hongpaisan, J., Sun, M. K., and Alkon, D. L. (2011) PKC epsilon activation prevents synaptic loss, Abeta elevation, and cognitive deficits in Alzheimer's disease transgenic mice J. Neurosci. 31, 630-643 10.1523/JNEUROSCI.5209-10.2011
96. Keck, G. E., Poudel, Y. B., Cummins, T. J., Rudra, A., and Covel, J. A. (2011) Total synthesis of bryostatin 1 J. Am. Chem. Soc. 133, 744-747 10.1021/ja110198y
97. Lu, Y., Woo, S. K., and Krische, M. J. (2011) Total synthesis of bryostatin 7 via C-C bond-forming hydrogenation J. Am. Chem. Soc. 133, 13876-13879 10.1021/ja205673e
98. Wender, P. A. and Schrier, A. J. (2011) Total synthesis of bryostatin 9 J. Am. Chem. Soc. 133, 9228-9231 10.1021/ja203034k
99. 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 synthesis, folding, and phorbol ester binding of the cysteine-rich domains of all protein kinase C isozymes J. Am. Chem. Soc. 120, 9159-9167 10.1021/ja981087f
100. Ananthanarayanan, B., Stahelin, R. V., Digman, M. A., and Cho, W. H. (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 10.1074/jbc.M307853200
101. Pu, Y. M., Garfield, S. H., Kedei, N., and Blumberg, P. M. (2009) Characterization of the Differential Roles of the Twin C1a and C1b Domains of Protein Kinase C delta J. Biol. Chem. 284, 1302-1312 10.1074/jbc.M804796200
102. Slater, S. J., Ho, C., Kelly, M. B., Larkin, J. D., Taddeo, F. J., Yeager, M. D., and Stubbs, C. D. (1996) Protein kinase Calpha contains two activator binding sites that bind phorbol esters and diacylglycerols with opposite affinities J. Biol. Chem. 271, 4627-4631 10.1074/jbc.271.9.4627
103. Medkova, M. and Cho, W. H. (1999) Interplay of C1 and C2 domains of protein kinase C-alpha in its membrane binding and activation J. Biol. Chem. 274, 19852-19861 10.1074/jbc.274.28.19852
104. Szallasi, Z., Bogi, K., Gohari, S., Biro, T., Acs, P., and Blumberg, P. M. (1996) Non-equivalent roles for the first and second zinc fingers of protein kinase C delta-Effect of their mutation on phorbol ester-induced translocation in NIH 3T3 cells J. Biol. Chem. 271, 18299-18301 10.1074/jbc.271.31.18299
105. Stahelin, R. V., Digman, M. A., Medkova, M., Ananthanarayanan, B., Rafter, J. D., Melowic, H. R., and Cho, W. H. (2004) Mechanism of diacylglycerol-induced membrane targeting and activation of protein kinase C delta J. Biol. Chem. 279, 29501-29512 10.1074/jbc.M403191200
106. 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 Calpha J. Mol. Biol. 408, 949-970 10.1016/j.jmb.2011.03.020
107. Stewart, M. D. and Igumenova, T. I. (2012) Reactive Cysteine in the Structural Zn(2+) Site of the C1B Domain from PKCalpha Biochemistry 51, 7263-7277 10.1021/bi300750w
108. Korichneva, I., Hoyos, B., Chua, R., Levi, E., and Hammerling, U. (2002) Zinc release from protein kinase C as the common event during activation by lipid second messenger or reactive oxygen J. Biol. Chem. 277, 44327-44331 10.1074/jbc.M205634200
109. Medkova, M. and Cho, W. H. (1998) Differential membrane-binding and activation mechanisms of protein kinase C-alpha and -epsilon Biochemistry 37, 4892-4900 10.1021/bi972495j
110. Dries, D. R. and Newton, A. C. (2008) Kinetic analysis of the interaction of the C1 domain of protein kinase C with lipid membranes by stopped-flow spectroscopy J. Biol. Chem. 283, 7885-7893 10.1074/jbc.M709943200
111. Medkova, M. and Cho, W. (1999) Interplay of C1 and C2 domains of protein kinase C-alpha in its membrane binding and activation J. Biol. Chem. 274, 19852-19861 10.1074/jbc.274.28.19852
112. Mosior, M. and McLaughlin, S. (1991) Peptides that mimic the pseudosubstarte regionof protein kinase C bind to acidic lipids in membranes Biophys. J. 60, 149-159 10.1016/S0006-3495(91)82038-0
113. Oancea, E. and Meyer, T. (1998) Protein kinase C as a molecular machine for decoding calcium and diacylglycerol signals Cell 95, 307-318 10.1016/S0092-8674(00)81763-8
114. Gao, T., Toker, A., and Newton, A. C. (2001) The carboxyl terminus of protein kinase c provides a switch to regulate its interaction with the phosphoinositide-dependent kinase, PDK-1 J. Biol. Chem. 276, 19588-19596 10.1074/jbc.M101357200
115. Facchinetti, V., Ouyang, W., Wei, H., Soto, N., Lazorchak, A., Gould, C., Lowry, C., Newton, A. C., Mao, Y., Miao, R. Q., Sessa, W. C., Qin, J., Zhang, P., Su, B., and Jacinto, E. (2008) The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C EMBO J. 27, 1932-1943 10.1038/emboj.2008.120
116. Ikenoue, T., Inoki, K., Yang, Q., Zhou, X., and Guan, K. L. (2008) Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling EMBO J. 27, 1919-1931 10.1038/emboj.2008.119
117. Behn-Krappa, A. and Newton, A. C. (1999) The hydrophobic phosphorylation motif of conventional protein kinase C is regulated by autophosphorylation Curr. Biol. 9, 728-737 10.1016/S0960-9822(99)80332-7
118. Staudinger, J., Lu, J. R., and Olson, E. N. (1997) Specific interaction of the PDZ domain protein PICK1 with the COOH terminus of protein kinase C-alpha J. Biol. Chem. 272, 32019-32024 10.1074/jbc.272.51.32019
119. Ammendrup-Johnsen, I., Thorsen, T. S., Gether, U., and Madsen, K. L. (2012) Serine 77 in the PDZ Domain of PICK1 Is a Protein Kinase C alpha Phosphorylation Site Regulated by Lipid Membrane Binding Biochemistry 51, 586-596 10.1021/bi2014689
120. Stebbins, E. G. and Mochly-Rosen, D. (2001) Binding specificity for RACK1 resides in the V5 region of beta II protein kinase C J. Biol. Chem. 276, 29644-29650 10.1074/jbc.M101044200
121. Abrahamsen, H., O'Neill, A. K., Kannan, N., Kruse, N., Taylor, S. S., Jennings, P. A., and Newton, A. C. (2012) Peptidyl-prolyl Isomerase Pin1 Controls Down-regulation of Conventional Protein Kinase C Isozymes J. Biol. Chem. 287, 13262-13278 10.1074/jbc.M112.349753
122. Xu, Z. B., Chaudhary, D., Olland, S., Wolfrom, S., Czerwinski, R., Malakian, K., Lin, L., Stahl, M. L., Joseph-McCarthy, D., Benander, C., Fitz, L., Greco, R., Somers, W. S., and Mosyak, L. (2004) Catalytic domain crystal structure of protein kinase C-theta (PKCtheta) J. Biol. Chem. 279, 50401-50409 10.1074/jbc.M409216200
123. Messerschmidt, A., Macieira, S., Velarde, M., Badeker, M., Benda, C., Jestel, A., Brandstetter, H., Neuefeind, T., and Blaesse, M. (2005) Crystal structure of the catalytic domain of human atypical protein kinase C-iota reveals interaction mode of phosphorylation site in turn motif J. Mol. Biol. 352, 918-931 10.1016/j.jmb.2005.07.060
124. Takimura, T., Kamata, K., Fukasawa, K., Ohsawa, H., Komatani, H., Yoshizumi, T., Takahashi, I., Kotani, H., and Iwasawa, Y. (2010) Structures of the PKC-iota kinase domain in its ATP-bound and apo forms reveal defined structures of residues 533-551 in the C-terminal tail and their roles in ATP binding Acta Crystallogr., Sect. D: Biol. Crystallogr. 66, 577-583 10.1107/S0907444910005639
125. Wagner, J., von Matt, P., Sedrani, R., Albert, R., Cooke, N., Ehrhardt, C., Geiser, M., Rummel, G., Stark, W., Strauss, A., Cowan-Jacob, S. W., Beerli, C., Weckbecker, G., Evenou, J. P., Zenke, G., and Cottens, S. (2009) Discovery of 3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione (AEB071), a potent and selective inhibitor of protein kinase C isotypes J. Med. Chem. 52, 6193-6196 10.1021/jm901108b
126. Grodsky, N., Li, Y., Bouzida, D., Love, R., Jensen, J., Nodes, B., Nonomiya, J., and Grant, S. (2006) Structure of the catalytic domain of human protein kinase C beta II complexed with a bisindolylmaleimide inhibitor Biochemistry 45, 13970-13981 10.1021/bi061128h
127. George, D. M., Breinlinger, E. C., Argiriadi, M. A., Zhang, Y., Wang, J. F., Bansal-Pakala, P., Duignan, D. B., Honore, P., Lang, Q. Y., Mittelstadt, S., Rundell, L., Schwartz, A., Sun, J. K., and Edmunds, J. J. (2015) Optimized Protein Kinase C theta (PKC theta) Inhibitors Reveal Only Modest Anti-inflammatory Efficacy in a Rodent Model of Arthritis J. Med. Chem. 58, 333-346 10.1021/jm5013006
128. George, D. M., Breinlinger, E. C., Friedman, M., Zhang, Y., Wang, J. F., Argiriadi, M., Bansal-Pakala, P., Barth, M., Duignan, D. B., Honore, P., Lang, Q. Y., Mittelstadt, S., Potin, D., Rundell, L., and Edmunds, J. J. (2015) Discovery of Selective and Orally Bioavailable Protein Kinase C theta (PKC theta) Inhibitors from a Fragment Hit J. Med. Chem. 58, 222-236 10.1021/jm500669m
129. Kjaer, S., Linch, M., Purkiss, A., Kostelecky, B., Knowles, P. P., Rosse, C., Riou, P., Soudy, C., Kaye, S., Patel, B., Soriano, E., Murray-Rust, J., Barton, C., Dillon, C., Roffey, J., Parker, P. J., and McDonald, N. Q. (2013) Adenosine-binding motif mimicry and cellular effects of a thieno 2,3-d pyrimidine-based chemical inhibitor of atypical protein kinase C isoenzymes Biochem. J. 451, 329-342 10.1042/BJ20121871
130. van Eis, M. J., Evenou, J. P., Floersheim, P., Gaul, C., Cowan-Jacob, S. W., Monovich, L., Rummel, G., Schuler, W., Stark, W., Strauss, A., von Matt, A., Vangrevelinghe, E., Wagner, J., and Soldermann, N. (2011) 2,6-Naphthyridines as potent and selective inhibitors of the novel protein kinase C isozymes Bioorg. Med. Chem. Lett. 21, 7367-7372 10.1016/j.bmcl.2011.10.025
131. Wang, C. H., Shang, Y., Yu, J., and Zhang, M. J. (2012) Substrate Recognition Mechanism of Atypical Protein Kinase Cs Revealed by the Structure of PKC iota in Complex with a Substrate Peptide from Par-3 Structure 20, 791-801 10.1016/j.str.2012.02.022
132. Yang, Y. and Igumenova, T. I. (2013) The C-Terminal V5 Domain of Protein Kinase C alpha Is Intrinsically Disordered, with Propensity to Associate with a Membrane Mimetic PLoS One 8, e65699 10.1371/journal.pone.0065699
133. Marsh, J. A., Singh, V. K., Jia, Z., and Forman-Kay, J. D. (2006) Sensitivity of secondary structure propensities to sequence differences between alpha- and gamma-synuclein: implications for fibrillation Protein Sci. 15, 2795-2804 10.1110/ps.062465306
134. Farrow, N. A., Zhang, O., Szabo, A., Torchia, D. A., and Kay, L. E. (1995) Spectral density function mapping using 15N relaxation data exclusively J. Biomol. NMR 6, 153-162 10.1007/BF00211779
135. Peng, J. W. and Wagner, G. (1992) Mapping of spectral density functions using heteronuclear NMR relaxation measurements J. Magn. Reson. 98, 308-332 10.1016/0022-2364(92)90135-T
136. Dyson, H. J. and Wright, P. E. (2004) Unfolded proteins and protein folding studied by NMR Chem. Rev. 104, 3607-3622 10.1021/cr030403s
137. Eisenberg, D., Weiss, R. M., and Terwilliger, T. C. (1982) The helical hydrophobic moment-a measure of the amphiphilicity of a helix Nature 299, 371-374 10.1038/299371a0
138. Rice, P., Longden, I., and Bleasby, A. (2000) EMBOSS: The European molecular biology open software suite Trends Genet. 16, 276-277 10.1016/S0168-9525(00)02024-2
139. Sonnenburg, E. D., Gao, T., and Newton, A. C. (2001) The phosphoinositide-dependent kinase, PDK-1, phosphorylates conventional protein kinase C isozymes by a mechanism that is independent of phosphoinositide 3-kinase J. Biol. Chem. 276, 45289-45297 10.1074/jbc.M107416200
140. Newton, A. C. (2003) Regulation of the ABC kinases by phosphorylation: protein kinase C as a paradigm Biochem. J. 370, 361-371 10.1042/BJ20021626