Protein kinase C in the immune system: From signalling to chromatin regulation

Immunology

Volumn 146, Issue 4, 2015, Pages 508-522

  Lim, Pek Siew ^a   Sutton, Christopher Ray ^a   Rao, Sudha ^a  

^a UNIVERSITY OF CANBERRA   (Australia)

Author keywords

Chromatin; Epigenetics; Immune system; Protein kinase C; Signal transduction

Indexed keywords

B LYMPHOCYTE RECEPTOR; PROTAMINE KINASE; PROTEIN KINASE C; PROTEIN KINASE C BETA; PROTEIN KINASE C EPSILON; PROTEIN KINASE C THETA; SERINE; T LYMPHOCYTE RECEPTOR; THREONINE; TOLL LIKE RECEPTOR 4; TRANSCRIPTION FACTOR; CHROMATIN; HISTONE; ISOPROTEIN; PROTEIN BINDING;

ADAPTIVE IMMUNITY; ARTICLE; CELL MEMBRANE; CELL NUCLEUS; CELL PROLIFERATION; CHROMATIN; CYTOPLASM; ENZYME PHOSPHORYLATION; GENE EXPRESSION; GENE EXPRESSION REGULATION; HUMAN; IMMUNE SYSTEM; IMMUNOCOMPETENT CELL; IMMUNOLOGICAL SYNAPSE; INNATE IMMUNITY; INTRACELLULAR SIGNALING; NONHUMAN; NUCLEAR LOCALIZATION SIGNAL; PRIORITY JOURNAL; ANIMAL; APOPTOSIS; CHROMATIN ASSEMBLY AND DISASSEMBLY; GENETIC EPIGENESIS; GENETICS; IMMUNOLOGY; LYMPHOCYTE ACTIVATION; METABOLISM; PHYSIOLOGY; PROTEIN TRANSPORT; SIGNAL TRANSDUCTION; T LYMPHOCYTE;

ANIMALS; APOPTOSIS; CELL NUCLEUS; CHROMATIN; CHROMATIN ASSEMBLY AND DISASSEMBLY; CYTOPLASM; EPIGENESIS, GENETIC; GENE EXPRESSION REGULATION; HISTONES; HUMANS; IMMUNE SYSTEM; LYMPHOCYTE ACTIVATION; PROTEIN BINDING; PROTEIN ISOFORMS; PROTEIN KINASE C; PROTEIN TRANSPORT; SIGNAL TRANSDUCTION; T-LYMPHOCYTES;

EID: 84983161143     PISSN: 00192805     EISSN: 13652567     Source Type: Journal    
DOI: 10.1111/imm.12510     Document Type: Article

References (154)

1. Keenan C, Long A, Kelleher D. Protein kinase C and T cell function. Biochim Biophys Acta 1997; 1358:113-26.
2. Newton AC. Protein kinase C: structural and spatial regulation by phosphorylation, cofactors, and macromolecular interactions. Chem Rev 2001; 101:2353-64.
3. Nalefski EA, Falke JJ. The C2 domain calcium-binding motif: structural and functional diversity. Protein Sci 1996; 5:2375-90.
4. Giorgione JR, Lin JH, McCammon JA, Newton AC. 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 2006; 281:1660-9.
5. Puls A, Schmidt S, Grawe F, Stabel S. Interaction of protein kinase C zeta with ZIP, a novel protein kinase C-binding protein. Proc Natl Acad Sci U S A 1997; 94:6191-6.
6. Newton AC. Protein kinase C: structure, function, and regulation. J Biol Chem 1995; 270:28495-8.
7. Loegering DJ, Lennartz MR. Protein kinase C and toll-like receptor signaling. Enzyme Res 2011; 2011:537821.
8. Isakov N, Altman A. Protein kinase Cθ in T cell activation. Annu Rev Immunol 2002; 20:761-94.
9. Altman A, Kong KF. Protein kinase C inhibitors for immune disorders. Drug Discov Today 2014; 19:1217-21.
10. Lee MS, Kim YJ. Signaling pathways downstream of pattern-recognition receptors and their cross talk. Annu Rev Biochem 2007; 76:447-80.
11. West AP, Koblansky AA, Ghosh S. Recognition and signaling by toll-like receptors. Annu Rev Cell Dev Biol 2006; 22:409-37.
12. Miyake K. Innate recognition of lipopolysaccharide by Toll-like receptor 4-MD-2. Trends Microbiol 2004; 12:186-92.
13. Yamamoto M, Sato S, Hemmi H et al. TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway. Nat Immunol 2003; 4:1144-50.
14. Gay NJ, Gangloff M. Structure and function of Toll receptors and their ligands. Annu Rev Biochem 2007; 76:141-65.
15. Kang JY, Lee JO. Structural biology of the Toll-like receptor family. Annu Rev Biochem 2011; 80:917-41.
16. Castrillo A, Pennington DJ, Otto F, Parker PJ, Owen MJ, Boscá L. Protein kinase Cε is required for macrophage activation and defense against bacterial infection. J Exp Med 2001; 194:1231-42.
17. Faisal A, Saurin A, Gregory B, Foxwell B, Parker PJ. The scaffold MyD88 acts to couple protein kinase Cε to Toll-like receptors. J Biol Chem 2008; 283:18591-600.
18. McGettrick AF, Brint EK, Palsson-McDermott EM, Rowe DC, Golenbock DT, Gay NJ, Fitzgerald KA, O'Neill LA. Trif-related adapter molecule is phosphorylated by PKCε during Toll-like receptor 4 signaling. Proc Natl Acad Sci U S A 2006; 103:9196-201.
19. Fitzgerald KA, Rowe DC, Barnes BJ et al. LPS-TLR4 signaling to IRF-3/7 and NF-κB involves the toll adapters TRAM and TRIF. J Exp Med 2003; 198:1043-55.
20. Medzhitov R, Preston-Hurlburt P, Janeway CA Jr. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 1997; 388:394-7.
21. Kawai T, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity 2011; 34:637-50.
22. Schnare M, Barton GM, Holt AC, Takeda K, Akira S, Medzhitov R. Toll-like receptors control activation of adaptive immune responses. Nat Immunol 2001; 2:947-50.
23. Acuto O, Cantrell D. T cell activation and the cytoskeleton. Annu Rev Immunol 2000; 18:165-84.
24. Diehn M, Alizadeh AA, Rando OJ, Liu CL, Stankunas K, Botstein D, Crabtree GR, Brown PO. Genomic expression programs and the integration of the CD28 costimulatory signal in T cell activation. Proc Natl Acad Sci U S A 2002; 99:11796-801.
25. Favero J, Lafont V. Effector pathways regulating T cell activation. Biochem Pharmacol 1998; 56:1539-47.
26. Smith-Garvin JE, Koretzky GA, Jordan MS. T cell activation. Annu Rev Immunol 2009; 27:591-619.
27. Fooksman DR, Vardhana S, Vasiliver-Shamis G et al. Functional anatomy of T cell activation and synapse formation. Annu Rev Immunol 2010; 28:79-105.
28. Yokosuka T, Saito T. The immunological synapse, TCR microclusters, and T cell activation. Curr Top Microbiol Immunol 2010; 340:81-107.
29. Kong K-F, Altman A. In and out of the bull's eye: protein kinase Cs in the immunological synapse. Trends Immunol 2013; 34:234-42.
30. Monks CR, Kupfer H, Tamir I, Barlow A, Kupfer A. Selective modulation of protein kinase C-theta during T-cell activation. Nature 1997; 385:83-6.
31. Baier G, Telford D, Giampa L, Coggeshall KM, Baier-Bitterlich G, Isakov N, Altman A. Molecular cloning and characterization of PKC θ, a novel member of the protein kinase C (PKC) gene family expressed predominantly in hematopoietic cells. J Biol Chem 1993; 268:4997-5004.
32. Monks CR, Freiberg BA, Kupfer H, Sciaky N, Kupfer A. Three-dimensional segregation of supramolecular activation clusters in T cells. Nature 1998; 395:82-6.
33. Huang J, Lo PF, Zal T, Gascoigne NR, Smith BA, Levin SD, Grey HM. CD28 plays a critical role in the segregation of PKC θ within the immunologic synapse. Proc Natl Acad Sci U S A 2002; 99:9369-73.
34. Kong KF, Yokosuka T, Canonigo-Balancio AJ, Isakov N, Saito T, Altman A. A motif in the V3 domain of the kinase PKC-θ determines its localization in the immunological synapse and functions in T cells via association with CD28. Nat Immunol 2011; 12:1105-12.
35. Yokosuka T, Kobayashi W, Sakata-Sogawa K, Takamatsu M, Hashimoto-Tane A, Dustin ML, Tokunaga M, Saito T. Spatiotemporal regulation of T cell costimulation by TCR-CD28 microclusters and protein kinase C θ translocation. Immunity 2008; 29:589-601.
36. von Essen MR, Kongsbak M, Levring TB et al. PKC-θ exists in an oxidized inactive form in naive human T cells. Eur J Immunol 2013; 43:1659-66.
37. Sun Z, Arendt CW, Ellmeier W et al. PKC-θ is required for TCR-induced NF-κB activation in mature but not immature T lymphocytes. Nature 2000; 404:402-7.
38. Anderson K, Fitzgerald M, Dupont M et al. Mice deficient in PKC θ demonstrate impaired in vivo T cell activation and protection from T cell-mediated inflammatory diseases. Autoimmunity 2006; 39:469-78.
39. 2+ mobilization and NFAT cell activation in primary mouse T cells. J Exp Med 2003; 197:1525-35.
40. Marsland BJ, Soos TJ, Spath G, Littman DR, Kopf M. 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 2004; 200:181-9.
41. Salek-Ardakani S, So T, Halteman BS, Altman A, Croft M. Protein kinase Cθ controls Th1 cells in experimental autoimmune encephalomyelitis. J Immunol 2005; 175:7635-41.
42. Tan SL, Zhao J, Bi C et al. Resistance to experimental autoimmune encephalomyelitis and impaired IL-17 production in protein kinase C θ-deficient mice. J Immunol 2006; 176:2872-9.
43. Kwon MJ, Ma J, Ding Y, Wang R, Sun Z. Protein kinase C-θ promotes Th17 differentiation via upregulation of Stat3. J Immunol 2012; 188:5887-97.
44. + Th17 cells. PLoS ONE 2014; 9:e96401.
45. + T cell effector and memory responses. Proc Natl Acad Sci U S A 2005; 102:14374-9.
46. Marsland BJ, Kopf M. T-cell fate and function: PKC-θ and beyond. Trends Immunol 2008; 29:179-85.
47. + memory versus effector development. Science 2009; 323:502-5.
48. Gupta S, Manicassamy S, Vasu C, Kumar A, Shang W, Sun Z. Differential requirement of PKC-θ in the development and function of natural regulatory T cells. Mol Immunol 2008; 46:213-24.
49. Zanin-Zhorov A, Ding Y, Kumari S et al. Protein kinase C-θ mediates negative feedback on regulatory T cell function. Science 2010; 328:372-6.
50. Ma J, Ding Y, Fang X, Wang R, Sun Z. Protein kinase C-θ inhibits inducible regulatory T cell differentiation via an AKT-Foxo1/3a-dependent pathway. J Immunol 2012; 188:5337-47.
51. Harwood NE, Batista FD. New insights into the early molecular events underlying B cell activation. Immunity 2008; 28:609-19.
52. Harwood NE, Batista FD. Early events in B cell activation. Annu Rev Immunol 2010; 28:185-210.
53. Packard TA, Cambier JC. B lymphocyte antigen receptor signaling: initiation, amplification, and regulation. F1000Prime Rep 2013; 5:40.
54. Mischak H, Kolch W, Goodnight J, Davidson WF, Rapp U, Rose-John S, Mushinski JF. Expression of protein kinase C genes in hemopoietic cells is cell-type- and B cell-differentiation stage specific. J Immunol 1991; 147:3981-7.
55. Brick-Ghannam C, Ericson ML, Schelle I, Charron D. Differential regulation of mRNAs encoding protein kinase C isoenzymes in activated human B cells. Hum Immunol 1994; 41:216-24.
56. Su TT, Guo B, Kawakami Y et al. PKC-β controls I κB kinase lipid raft recruitment and activation in response to BCR signaling. Nat Immunol 2002; 3:780-6.
57. Saijo K. Protein kinase C β controls nuclear factor κB activation in B cells through selective regulation of the IκB kinase α. J Exp Med 2002; 195:1647-52.
58. Leitges M, Schmedt C, Guinamard R, Davoust J, Schaal S, Stabel S, Tarakhovsky A. Immunodeficiency in protein kinase cβ-deficient mice. Science 1996; 273:788-91.
59. Fruman DA, Satterthwaite AB, Witte ON. Xid-like phenotypes: a B cell signalosome takes shape. Immunity 2000; 13:1-3.
60. Petro JB, Rahman SM, Ballard DW, Khan WN. Bruton's tyrosine kinase is required for activation of IκB kinase and nuclear factor κB in response to B cell receptor engagement. J Exp Med 2000; 191:1745-54.
61. Bajpai UD, Zhang K, Teutsch M, Sen R, Wortis HH. Bruton's tyrosine kinase links the B cell receptor to nuclear factor κB activation. J Exp Med 2000; 191:1735-44.
62. Kang SW, Wahl MI, Chu J et al. PKCβ modulates antigen receptor signaling via regulation of Btk membrane localization. EMBO J 2001; 20:5692-702.
63. Venkataraman C, Chen XC, Na S, Lee L, Neote K, Tan SL. Selective role of PKCβ enzymatic function in regulating cell survival mediated by B cell antigen receptor cross-linking. Immunol Lett 2006; 105:83-9.
64. Teh CE, Horikawa K, Arnold CN et al. Heterozygous mis-sense mutations in Prkcb as a critical determinant of anti-polysaccharide antibody formation. Genes Immun 2013; 14:223-33.
65. Shinohara H, Maeda S, Watarai H, Kurosaki T. IκB kinase β-induced phosphorylation of CARMA1 contributes to CARMA1 Bcl10 MALT1 complex formation in B cells. J Exp Med 2007; 204:3285-93.
66. Shinohara H, Yasuda T, Aiba Y, Sanjo H, Hamadate M, Watarai H, Sakurai H, Kurosaki T. PKC β regulates BCR-mediated IKK activation by facilitating the interaction between TAK1 and CARMA1. J Exp Med 2005; 202:1423-31.
67. Sommer K, Guo B, Pomerantz JL, Bandaranayake AD, Moreno-Garcia ME, Ovechkina YL, Rawlings DJ. Phosphorylation of the CARMA1 linker controls NF-κB activation. Immunity 2005; 23:561-74.
68. Capitani S, Girard PR, Mazzei GJ, Kuo JF, Berezney R, Manzoli FA. Immunochemical characterization of protein kinase C in rat liver nuclei and subnuclear fractions. Biochem Biophys Res Commun 1987; 142:367-75.
69. Beckmann R, Lindschau C, Haller H, Hucho F, Buchner K. Differential nuclear localization of protein kinase C isoforms in neuroblastoma × glioma hybrid cells. Eur J Biochem 1994; 222:335-43.
70. Disatnik MH, Buraggi G, Mochly-Rosen D. Localization of protein kinase C isozymes in cardiac myocytes. Exp Cell Res 1994; 210:287-97.
71. Martelli AM, Sang N, Borgatti P, Capitani S, Neri LM. Multiple biological responses activated by nuclear protein kinase C. J Cell Biochem 1999; 74:499-521.
72. Raben DM, Jarpe MB, Leach KL. Nuclear lipid metabolism in NEST: Nuclear Envelope Signal Transduction. J Membr Biol 1994; 142:1-7.
73. Whetton AD, Heyworth CM, Nicholls SE, Evans CA, Lord JM, Dexter TM, Owen-Lynch PJ. Cytokine-mediated protein kinase C activation is a signal for lineage determination in bipotential granulocyte macrophage colony-forming cells. J Cell Biol 1994; 125:651-9.
74. Mallia CM, Aguirre V, McGary E, Tang Y, Scandurro AB, Liu C, Noguchi CT, Beckman BS. Protein kinase cα is an effector of hexamethylene bisacetamide-induced differentiation of Friend erythroleukemia cells. Exp Cell Res 1999; 246:348-54.
75. Buchner K. The role of protein kinase C in the regulation of cell growth and in signalling to the cell nucleus. J Cancer Res Clin Oncol 2000; 126:1-11.
76. Zauli G, Visani G, Bassini A et al. Nuclear translocation of protein kinase C-α and -ζ isoforms in HL-60 cells induced to differentiate along the granulocytic lineage by all-trans retinoic acid. Br J Haematol 1996; 93:542-50.
77. Bertolaso L, Gibellini D, Secchiero P et al. Accumulation of catalytically active PKC-ζ into the nucleus of HL-60 cell line plays a key role in the induction of granulocytic differentiation mediated by all-trans retinoic acid. Br J Haematol 1998; 100:541-9.
78. Owen PJ, Johnson GD, Lord JM. Protein kinase C-δ associates with vimentin intermediate filaments in differentiated HL60 cells. Exp Cell Res 1996; 225:366-73.
79. Echevarria W, Leite MF, Guerra MT, Zipfel WR, Nathanson MH. Regulation of calcium signals in the nucleus by a nucleoplasmic reticulum. Nat Cell Biol 2003; 5:440-6.
80. Irvine RF. Nuclear lipid signaling. Sci STKE 2002; 2002:re13.
81. Neri LM, Bortul R, Borgatti P, Tabellini G, Baldini G, Capitani S, Martelli AM. Proliferating or differentiating stimuli act on different lipid-dependent signaling pathways in nuclei of human leukemia cells. Mol Biol Cell 2002; 13:947-64.
82. Rosenberger U, Lehmann I, Weise C, Franke P, Hucho F, Buchner K. Identification of PSF as a protein kinase Cα-binding protein in the cell nucleus. J Cell Biochem 2002; 86:394-402.
83. Macara IG. Transport into and out of the nucleus. Microbiol Mol Biol Rev 2001; 65:570-94, table of contents.
84. McLane LM, Corbett AH. Nuclear localization signals and human disease. IUBMB Life 2009; 61:697-706.
85. Malviya AN, Block C. A bipartite nuclear targeting motif in protein kinase C? Trends Biochem Sci 1992; 17:176.
86. DeVries TA, Neville MC, Reyland ME. Nuclear import of PKCδ is required for apoptosis: identification of a novel nuclear import sequence. EMBO J 2002; 21:6050-60.
87. Adwan TS, Ohm AM, Jones DNM, Humphries MJ, Reyland ME. Regulated binding of importin-α to protein kinase Cδ in response to apoptotic signals facilitates nuclear import. J Biol Chem 2011; 286:35716-24.
88. Perander M, Bjørkøy G, Johansen T. Nuclear import and export signals enable rapid nucleocytoplasmic shuttling of the atypical protein kinase C λ. J Biol Chem 2001; 276:13015-24.
89. White WO, Seibenhener ML, Wooten MW. Phosphorylation of tyrosine 256 facilitates nuclear import of atypical protein kinase C. J Cell Biochem 2002; 85:42-53.
90. Schmalz D, Kalkbrenner F, Hucho F, Buchner K. Transport of protein kinase C α into the nucleus requires intact cytoskeleton while the transport of a protein containing a canonical nuclear localization signal does not. J Cell Sci 1996; 109(Pt 9):2401-6.
91. Schmalz D, Hucho F, Buchner K. Nuclear import of protein kinase C occurs by a mechanism distinct from the mechanism used by proteins with a classical nuclear localization signal. J Cell Sci 1998; 111(Pt 13):1823-30.
92. Seidl S, Braun UB, Leitges M. Functional comparison of protein domains within aPKCs involved in nucleocytoplasmic shuttling. Biol Open 2012; 1:436-45.
93. Chuderland D, Konson A, Seger R. Identification and characterization of a general nuclear translocation signal in signaling proteins. Mol Cell 2008; 31:850-61.
94. Sutcliffe EL, Li J, Zafar A et al. Chromatinized protein kinase C-θ: can it escape the clutches of NF-κB? Front Immunol 2012; 3:260.
95. Wagner S, Harteneck C, Hucho F, Buchner K. Analysis of the subcellular distribution of protein kinase Cα using PKC-GFP fusion proteins. Exp Cell Res 2000; 258:204-14.
96. Eldar H, Livneh E. Phosphorylation of p90 and p52 in response to phorbol-esters in Swiss/3T3 cells overexpressing protein kinase C-α. Mol Biol Cell 1992; 3:1049-56.
97. Buchner K. Protein kinase C in the transduction of signals toward and within the cell nucleus. Eur J Biochem 1995; 228:211-21.
98. Martelli AM, Evangelisti C, Nyakern M, Manzoli FA. Nuclear protein kinase C. Biochim Biophys Acta 2006; 1761:542-51.
99. Kornberg RD, Lorch Y. Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell 1999; 98:285-94.
100. Misteli T, Gunjan A, Hock R, Bustin M, Brown DT. Dynamic binding of histone H1 to chromatin in living cells. Nature 2000; 408:877-81.
101. Lim PS, Li J, Holloway AF, Rao S. Epigenetic regulation of inducible gene expression in the immune system. Immunology 2013; 139:285-93.
102. Lim PS, Shannon MF, Hardy K. Epigenetic control of inducible gene expression in the immune system. Epigenomics 2010; 2:775-95.
103. Lee TI, Young RA. Transcription of eukaryotic protein-coding genes. Annu Rev Genet 2000; 34:77-137.
104. Alepuz PM, Jovanovic A, Reiser V, Ammerer G. Stress-induced map kinase Hog1 is part of transcription activation complexes. Mol Cell 2001; 7:767-77.
105. Baek SH. When signaling kinases meet histones and histone modifiers in the nucleus. Mol Cell 2011; 42:274-84.
106. Varin MM, Guerrier T, Devauchelle-Pensec V, Jamin C, Youinou P, Pers JO. In Sjogren's syndrome, B lymphocytes induce epithelial cells of salivary glands into apoptosis through protein kinase C δ activation. Autoimmun Rev 2012; 11:252-8.
107. Mecklenbrauker I, Kalled SL, Leitges M, Mackay F, Tarakhovsky A. Regulation of B-cell survival by BAFF-dependent PKCδ-mediated nuclear signalling. Nature 2004; 431:456-61.
108. Hurd PJ, Bannister AJ, Halls K et al. Phosphorylation of histone H3 Thr-45 is linked to apoptosis. J Biol Chem 2009; 284:16575-83.
109. Park CH, Kim KT. Apoptotic phosphorylation of histone H3 on Ser-10 by protein kinase Cδ. PLoS ONE 2012; 7:e44307.
110. Basu A, Pal D. Two faces of protein kinase Cδ: the contrasting roles of PKCδ in cell survival and cell death. ScientificWorldJournal 2010; 10:2272-84.
111. Granja AG, Perkins ND, Revilla Y. A238L inhibits NF-ATc2, NF-κB, and c-Jun activation through a novel mechanism involving protein kinase C-θ-mediated up-regulation of the amino-terminal transactivation domain of p300. J Immunol 2008; 180:2429-42.
112. Sutcliffe EL, Bunting KL, He YQ et al. Chromatin-associated protein kinase C-θ regulates an inducible gene expression program and microRNAs in human T lymphocytes. Mol Cell 2011; 41:704-19.
113. Zafar A, Wu F, Hardy K et al. Chromatinized protein kinase C-θ directly regulates inducible genes in epithelial to mesenchymal transition and breast cancer stem cells. Mol Cell Biol 2014; 34:2961-80.
114. Wang Y, Mo X, Piper MG, Wang H, Parinandi NL, Guttridge D, Marsh CB. M-CSF induces monocyte survival by activating NF-κB p65 phosphorylation at Ser276 via protein kinase C. PLoS ONE 2011; 6:e28081.
115. Levy D, Kuo AJ, Chang Y et al. Lysine methylation of the NF-κB subunit RelA by SETD6 couples activity of the histone methyltransferase GLP at chromatin to tonic repression of NF-κB signaling. Nat Immunol 2011; 12:29-36.
116. Kang JW, Park YS, Kim MS et al. Interleukin (IL)-32β-mediated CCAAT/enhancer-binding protein α (C/EBPα) phosphorylation by protein kinase Cδ (PKCδ) abrogates the inhibitory effect of C/EBPα on IL-10 production. J Biol Chem 2013; 288:23650-8.
117. Cheng MB, Zhang Y, Zhong X et al. Stat1 mediates an auto-regulation of hsp90β gene in heat shock response. Cell Signal 2010; 22:1206-13.
118. Kwon MJ, Yao Y, Walter MJ, Holtzman MJ, Chang CH. Role of PKCδ in IFN-γ-inducible CIITA gene expression. Mol Immunol 2007; 44:2841-9.
119. Kwon MJ, Soh JW, Chang CH. Protein kinase C δ is essential to maintain CIITA gene expression in B cells. J Immunol 2006; 177:950-6.
120. Blois JT, Mataraza JM, Mecklenbrauker I, Tarakhovsky A, Chiles TC. B cell receptor-induced cAMP-response element-binding protein activation in B lymphocytes requires novel protein kinase Cδ. J Biol Chem 2004; 279:30123-32.
121. Solomou EE, Juang YT, Tsokos GC. Protein kinase C-θ participates in the activation of cyclic AMP-responsive element-binding protein and its subsequent binding to the -180 site of the IL-2 promoter in normal human T lymphocytes. J Immunol 2001; 166:5665-74.
122. Pavan Kumar P, Purbey PK, Sinha CK, Notani D, Limaye A, Jayani RS, Galande S. Phosphorylation of SATB1, a global gene regulator, acts as a molecular switch regulating its transcriptional activity in vivo. Mol Cell 2006; 22:231-43.
123. Lee JM, Kim IS, Kim H et al. RORα attenuates Wnt/β-catenin signaling by PKCα-dependent phosphorylation in colon cancer. Mol Cell 2010; 37:183-95.
124. Zhang XH, Zheng B, Gu C, Fu JR, Wen JK. TGF-β1 downregulates AT1 receptor expression via PKC-δ-mediated Sp1 dissociation from KLF4 and Smad-mediated PPAR-iγ association with KLF4. Arterioscler Thromb Vasc Biol 2012; 32:1015-23.
125. Liokatis S, Stutzer A, Elsasser SJ et al. Phosphorylation of histone H3 Ser10 establishes a hierarchy for subsequent intramolecular modification events. Nat Struct Mol Biol 2012; 19:819-23.
126. Metzger E, Imhof A, Patel D et al. Phosphorylation of histone H3T6 by PKCβI controls demethylation at histone H3K4. Nature 2010; 464:792-6.
127. Gustafsson Sheppard N, Heldring N, Dahlman-Wright K. Estrogen receptor-α, RBCK1, and protein kinase C β1 cooperate to regulate estrogen receptor-α gene expression. J Mol Endocrinol 2012; 49:277-87.
128. Mochly-Rosen D, Das K, Grimes KV. Protein kinase C, an elusive therapeutic target? Nat Rev Drug Discov 2012; 11:937-57.
129. Salzer E, Santos-Valente E, Klaver S et al. B-cell deficiency and severe autoimmunity caused by deficiency of protein kinase C δ. Blood 2013; 121:3112-6.
130. Kuehn HS, Niemela JE, Rangel-Santos A et al. Loss-of-function of the protein kinase C δ (PKCδ) causes a B-cell lymphoproliferative syndrome in humans. Blood 2013; 121:3117-25.
131. Chen L, Hahn H, Wu G et al. Opposing cardioprotective actions and parallel hypertrophic effects of δ PKC and ε PKC. Proc Natl Acad Sci U S A 2001; 98:11114-9.
132. Sanchez-Bautista S, Nicolas FE. Recent patents concerning modulators of protein kinase C. Recent Pat DNA Gene Seq 2013; 7:74-81.
133. Zhang EY, Kong KF, Altman A. The yin and yang of protein kinase C-ζ (PKCζ): a novel drug target for selective immunosuppression. Adv Pharmacol 2013; 66:267-312.
134. He X, Koenen HJ, Smeets RL et al. Targeting PKC in human T cells using sotrastaurin (AEB071) preserves regulatory T cells and prevents IL-17 production. J Invest Dermatol 2014; 134:975-83.
135. Sommerer C, Zeier M. AEB071-a promising immunosuppressive agent. Clin Transplant 2009; 23(Suppl. 21):15-8.
136. Skvara H, Dawid M, Kleyn E et al. The PKC inhibitor AEB071 may be a therapeutic option for psoriasis. J Clin Invest 2008; 118:3151-9.
137. Budde K, Sommerer C, Becker T et al. Sotrastaurin, a novel small molecule inhibiting protein kinase C: first clinical results in renal-transplant recipients. Am J Transplant 2010; 10:571-81.
138. Friman S, Arns W, Nashan B et al. Sotrastaurin, a novel small molecule inhibiting protein-kinase C: randomized phase II study in renal transplant recipients. Am J Transplant 2011; 11:1444-55.
139. Jimenez JM, Boyall D, Brenchley G et al. Design and optimization of selective protein kinase C ζ (PKCζ) inhibitors for the treatment of autoimmune diseases. J Med Chem 2013; 56:1799-810.
140. Curnock A, Bolton C, Chiu P et al. Selective protein kinase Cθ (PKCθ) inhibitors for the treatment of autoimmune diseases. Biochem Soc Trans 2014; 42:1524-8.
141. Ron D, Luo J, Mochly-Rosen D. C2 region-derived peptides inhibit translocation and function of beta protein kinase C in vivo. J Biol Chem 1995; 270:24180-7.
142. Csukai M, Chen CH, De Matteis MA, Mochly-Rosen D. The coatomer protein β'-COP, a selective binding protein (RACK) for protein kinase Cε. J Biol Chem 1997; 272:29200-6.
143. Arruda S, Ho JL. IL-4 receptor signal transduction in human monocytes is associated with protein kinase C translocation. J Immunol 1992; 149:1258-64.
144. Wang Y, Schramek H, Dunn MJ. Cytosolic and nuclear mitogen-activated protein kinases are regulated by distinct mechanisms. Exp Cell Res 1996; 225:382-8.
145. Chiarini A, Whitfield JF, Armato U, Dal Pra I. Protein kinase C-β II Is an apoptotic lamin kinase in polyomavirus-transformed, etoposide-treated pyF111 rat fibroblasts. J Biol Chem 2002; 277:18827-39.
146. DeVries-Seimon TA, Ohm AM, Humphries MJ, Reyland ME. Induction of apoptosis is driven by nuclear retention of protein kinase C δ. J Biol Chem 2007; 282:22307-14.
147. Plotnikov A, Flores K, Maik-Rachline G et al. The nuclear translocation of ERK1/2 as an anticancer target. Nat Commun 2015; 6:6685.
148. -/- mice. J Immunol 2006; 176:6004-11.
149. Nechushtan H, Leitges M, Cohen C, Kay G, Razin E. Inhibition of degranulation and interleukin-6 production in mast cells derived from mice deficient in protein kinase Cβ. Blood 2000; 95:1752-7.
150. Miyamoto A, Nakayama K, Imaki H et al. Increased proliferation of B cells and auto-immunity in mice lacking protein kinase Cδ. Nature 2002; 416:865-9.
151. Fu G, Hu J, Niederberger-Magnenat N et al. Protein kinase C η is required for T cell activation and homeostatic proliferation. Sci Signal 2011; 4:ra84.
152. Kong KF, Fu G, Zhang Y et al. Protein kinase C-η controls CTLA-4-mediated regulatory T cell function. Nat Immunol 2014; 15:465-72.
153. Martin P, Duran A, Minguet S, Gaspar ML, Diaz-Meco MT, Rennert P, Leitges M, Moscat J. Role of ζ PKC in B-cell signaling and function. EMBO J 2002; 21:4049-57.
154. Soloff RS, Katayama C, Lin MY, Feramisco JR, Hedrick SM. Targeted deletion of protein kinase C λ reveals a distribution of functions between the two atypical protein kinase C isoforms. J Immunol 2004; 173:3250-60.