Protein kinase C-θ (PKC-θ) in natural killer cell function and anti-tumor immunity

Frontiers in Immunology

Volumn 3, Issue JUL, 2012, Pages

  Anel, Alberto ^a   Aguiló, Juan I ^a   Catalán, Elena ^a   Garaude, Johan ^b   Rathore, Moeez G ^b   Pardo, Julián ^a,c   Villalba, Martín ^b  

^a UNIVERSITY OF ZARAGOZA   (Spain)

^b INSERM   (France)

^c FUNDACIÓN ARAID   (Spain)

Author keywords

Anti tumor immunity; CTL; NK cells; PKC 8

Indexed keywords

EID: 84874263059     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2012.00187     Document Type: Review

References (126)

1. Aguilo, J. I., Garaude, J., Pardo, J., Villalba, M., and Anel, A. (2009). Protein kinase C-theta is required for NK cell activation and in vivo control of tumor progression. J. Immunol. 182, 1972-1981.
2. Akazawa, T., Ebihara, T., Okuno, M., Okuda, Y., Shingai, M., Tsujimura, K., Takahashi, T., Ikawa, M., Okabe, M., Inoue, N., Okamoto-Tanaka, M., Ishizaki, H., Miyoshi, J., Matsumoto, M., and Seya, T. (2007). Antitumor NK activation induced by the Tolllike receptor 3-TICAM-l (TRIF) pathway in myeloid dendritic cells. Proc. Natl. Acad. Sci. U.S.A. 104, 252-257.
3. Alderson, K. L, and Sondel, P. M. (2011). Clinical cancer therapy by NK cells via antibody-dependent cell-mediated cytotoxicity. J. Biomed. Biotechnol 2011, 379123.
4. Alexopoulou, L., Holt, A. C, Medzhitov, R., and Flavell, R. A. (2001). Recognition of double-stranded RNA and activation of NF-KappaB by Toll-like receptor 3. Nature 413, 732-738.
5. Altman, A., Kaminski, S., Busuttil, V., Droin, N., Hu, J., Tadevosyan, Y., Hipskind, R. A., and Villalba, M. (2004). Positive feedback regulation ofPLCyl/Ca2+ signaling by PKC6 in restimulated T cells via a Tec kinasedependent pathway. Eur. J. Immunol 34,2001-2011.
6. Anel, A., and Kleinfeld, A. M. (1993). Tyrosine phosphorylation of a 100 kDa protein is correlated with cytotoxic T-lymphocyte function. Evidence from cis unsaturated fatty acid and phenylarsineoxide inhibition. J. Biol. Chem. 268, 17578-17587.
7. Anel, A., Richieri, G. V., and Kleinfeld, A. M. (1994). A tyrosine phosphorylation requirement for cytotoxic T-lymphocyte degranulation. J. Biol. Chem. 269,9506-9513.
8. Anel, A., Simon, A. K., Auphan, N., Buferne, M., Boyer, C, Golstein, P., and Schmitt-Verhulst, A. M. (1995). Two signalling pathways can lead to Fas ligand expression in CD8+ cytotoxic T lymphocyte clones. Eur. J. Immunol. 25,3381-3387.
9. Aptsiauri, N., Cabrera, A., Garcia-Lora, A., Lopez-Nevoti, M. A., Ruiz-Cabello, E, and Garrido, E (2007). MHC class I antigens and immune surveillance in transformed cells. Int. Rev. Cytol. 256, 139-189.
10. Arneson, L., Brickshawana, A., Segovis, C, Schoon, R., Dick, C, and Leibson, P. J. (2007). Syntaxin 11 regulates lymphocyte-mediated secretion and cytotoxicity. J. Immunol. 179,3397-3401.
11. Baier, G., Telford, D., Giampa, K. M., Coggeshall, K. M., Baier-Bitterlich, G.,Isakov,N., and Altman, A. (1993). Molecular cloning and characterization of PKC9, a human novel member of the protein kinase C (PKC) gene family expressed predominantly in hematopoietic cells. J. Biol. Chem. 268, 4997-5004.
12. Baier-Bitterlich, G., Uberall, E, Bauer, B., Fresser, E, Wachter, H., Grunicke, H., Utermann, G., Altman, A., and Baier, G. (1996). Protein kinase C-0 isoenzyme selective stimulation of the transcription factor complex AP-1 in T lymphocytes. Mol. Cell. Biol. 16,1842-1850.
13. Balogh, G., de Boland, A. R., Boland, R., and Barja, P. (1999). Effect of l,25[OH](2)-vitamin D(3) on the activation of natural killer cells: role of protein kinase C and extracellular calcium. Exp. Mol. Pathol. 67, 63-74.
14. Barouch-Bentov, R., Lemmens, E. E., Hu, J., Janssen, E. M., Droin, N. M., Song, J., Schoenberger, S. P., and Altman, A. (2005). Protein kinase C-0 is an early survival factor required for differentiation of effector CD8+ T cells. J. Immunol. 175, 5126-5134.
15. Ben Ahmed, M., Belhadj Hmida, N., Moes, N., Buyse, S., Abledadhim, M., Louzir, H., and Cerf-Bensussan, N. (2009). IL-15 renders conventional lymphocytes resistant to suppressive functions of regulatory T cells through activation of the phosphatidylinositol 3-kinase pathway. J. Immunol. 182, 6763-6770.
16. Berg, N. N., Puente, L. G., Dawicki, W., and Ostergaard, H. L. (1998). Sustained TCR signaling is required for MAPK activation and degranulation by CTL. J. Immunol. 161, 2919-2924.
17. Bertolotto, C, Maulon, L., Filippa, N., Baier, G., and Auberger, P. (2000). Protein kinase C theta and epsilon promote T-cell survival by a rsk-dependent phosphorylation and inactivation of BAD. J. Biol. Chem. 275,37246-37250.
18. Bhatnagar, N., Hong, H. S., Krishnaswamy, J. K., Haghikia, A., Behrens, G. M., Schmidt, R. E., and Jacobs, R. (2010). Cytokineactivated NK cells inhibit PMN apoptosis and preserve their functional capacity. Blood 116, 1308-1316.
19. Billadeau, D. D., Upshaw, J. L., Schoon, R. A., Dick, C. J., and Leibson, P. J. (2003). NKG2D-DAP10 triggers human NK cell-mediated killing via a Syk-independent regulatory pathway. Nat. Immunol. 4, 557-564.
20. Bonnema, J. D., Karnitz, L. M., Schoon, R. A., Abraham, R. T., and Leibson, P. J. (1994). Fc receptor stimulation of phosphatidylinositol 3-kinase in natural killer cells is associated with protein kinase C-independent granule release and cell-mediated cytotoxicity. J. Exp. Med. 180, 1427-1435.
21. Brennan, P., Babage, J. W., Burgering, B. M. T., Gromer, B., Reif, K., and Cantrell, D. A. (1997). Phosphatidylinositol 3-kinase couples the interleukin-2 receptor to the cell cycle regulator E2F. Immunity 7, 679-689.
22. Bryceson, Y., March, M., Ljunggren, H., andLong,E. (2006). Synergy among receptors on resting NK cells for the activation of natural cytotoxicity and cytokine secretion. Blood 107, 159-166.
23. Bryceson, Y., Rudd, E., Zheng, C, Edner, J., Ma, D., Wood, S., Bechensteen, A., Boelens, J. J., Celkan, T., Farah, R. A., Hultenby, K., Winiarski, J., Roche, P. A., Nordenskjold, M., Henter, J. I., Long, E. O., and Ljunggren, H. G. (2007). Defective cytotoxic lymphocyte degranulation in syntaxin-11 deficient familial hemophagocytic lymphohistiocytosis 4 (FHL4) patients. Blood 110, 1906-1915.
24. Bryceson, Y. T., March, M., Barber, D. E, Ljunggren, H. G., and Long, E. O. (2005). Cytolytic granule polarization and degranulation controlled by different receptors in resting NK cells. J. Exp. Med. 202,1001-1012.
25. Carlin, L., Eleme, K., McCann, E, and Davis, D. (2001). Intercellular transfer and supramolecular organization of human leukocyte antigen C at inhibitory natural killer cell immune synapses. J. Exp. Med. 194, 1507-1517.
26. Carson, W. E., Giri, J. G., Lindemann, M. J., Linett, M. L., Ahdieh, M., Paxton, R., Anderson, D., Eisenmann, J., Grabstein, K., and Caligiuri, M. A. (1994).Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor. J. Exp. Med. 180, 1395-1403.
27. Cerwenka, A., and Lanier, L. L. (2001). Natural killer cells, viruses and cancer. Nat. Rev. Immunol. 1, 41-49.
28. Chan, A. C, Iwashima, M., Turck, C. W., and Weiss, A. (1992). ZAP-70: a 70 kd protein-tyrosine kinase that associates with the TCR t, chain. Cell 71, 649.
29. Chen, X., Allan, D. S., Krzewski, K., Ge, B., Koopcow, H., and Strominger, J. L. (2006). CD28-stimulated ERK2 phosphorylation is required for polarization of the microtubule organizing center and granules in YTS NK cells. Proc. Nail. Acad. Sci. U.S.A. 103, 10346-10351.
30. Cho, D., and Campana, D. (2009). Expansion and activation of natural killer cells for cancer immunotherapy. Korean J. Lab. Med. 29, 89-96.
31. Clark, R., and Griffiths, G. M. (2003). Lytic granules, secretory lysosomes and disease. Curr. Opin. Immunol. 15,516-521.
32. Clark, R. H., Stinchcombe, J. C, Day, A., Blott, E., Booth, S., Bossi, G., Hamblin, T., Davies, E. G., and Griffiths, G. M. (2003). AP3-dependent microtubule-mediated movement of lytic granules to the immunological synapse. Nat. Immunol. 4, 1111-1120.
33. Colucci, E, Schweighoffer, E., Tomasello, E., Turner, M., Ortaldo, J., Vivier, E., Tybulewicz, V., and Di Santo, J. (2002). Natural cytotoxicity uncoupled from the Syk and ZAP-70 intracellular kinases. Nat. Immunol. 3, 288-294.
34. Cooper, M. A., Fehniger, T. A., Van-Deusen, J. B., Waite, R. E., Liu, Y., Aguila, H. L., and Caligiuri, M. A. (2002). In vivo evidence for a dependence on interleukin 15 for survival of natural killer cells. Blood 100, 3633-3638.
35. Coudronniere, N., Villalba, M., Englund, N., and Altman, A. (2000). NF-kB activation induced by TCRJCD28 costimulation is mediated by PKC-6. Proc. Natl. Acad. Sci. U.S.A. 97, 3394-3399.
36. 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.
37. Davis, D., Chiu, I., Fassett, M., Cohen, G., Mandelboim, O., and Strominger, J. (1999). The human natural killer cell immune synapse. Proc. Natl. Acad. Sci. U.S.A. 96, 15062-15067.
38. de Saint Basille, G., Menasche, G., and Fischer, A. (2010). Molecular mechanisms of biogenesis and exocytosis of cytotoxic granules. Nat. Rev. Immunol. 11,568-579.
39. Dennehy, K. M., Klimosch, S. N., and Steinle, A. (2011). NKp80 uses an atypical hemi-ITAM to trigger NK cytotoxicity. J. Immunol. 186, 657-661.
40. Djeu, J. Y., Heinbaugh, J. A., Holden, H. T., and Herberman, R. B. (1979). Role of macrophages in the augmentation of mouse NK cell activity by Poly I:C and interferon. J. Immunol. 122,182-188.
41. Dunn, G. P., Bruce, A. T., Ikeda, H., Old, L. J., and Schreiber, R. D. (2002). Cancer immunoediting: from immunosurveillance to tumor escape. Nat. Immunol. 3, 991-998.
42. Dunn, G. P., Koebel, C. M., and Schreiber, R. D. (2006). Interferons, immunity and cancer immunoediting. Nat. Rev. Immunol. 6, 836-848.
43. Feldmann, J., Callebaut, I., Raposo, G., Certain, S., Bacq, D., Dumont, C, Lambert, N., Ouachee-Chardin, M., Chedeville, G., Tamary, H., Minard-Colin, V., Vilmer, E., Blanche, S., Le Deist, E, Fischer, A., and de Saint Basile.G. (2003). Muncl3-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3). Cell 115,461-473.
44. Felli, M., Vacca, A., Calce, A., Bellavia, D., Campese, A., Grillo, R., Di Giovine, M., Checquolo, S., Talora, C, Palermo, R., Di Mario, G., Frati, L., Gulino, A., and Screpanti, I. (2005). PKC thetamediates pre-TCR signaling and contributes to Notch3-induced T-cell leukemia. Oncogene 24,992-1000.
45. Garaude, J., Kaminski, S., Cherni, S., Aguilo, J. I., Jacquet, C, Plays, M., Rodriguez, F., Hernandez, J., Hipskind, R. A., Anel, A., and Villalba, M. (2008). Impaired anti-leukemic immune response in PKC9-deficient mice. Mol. Immunol. 45, 3463-3469.
46. Garrido, E, Algarra, I., and Garcia-Lora, A. (2010). The escape of cancer from T lymphocytes: immunoselection of MHC class I loss variants harboring structural-irreversible "hard" lesions. Cancer Immunol. Immunother. 59, 1601-1606.
47. Gomez, T. S., and Billadeau, D. D. (2008). T cell activation and the cytoskeleton: you can't have one without the other. Adv. Immunol. 97, 1-64.
48. Grybko, M. J., Pores-Fernando, A. T., Wurth, G. A., and Zweifach, A. (2007). Protein kinase C activity is required for cytotoxic T cell lytic granule exocytosis, but the 9 isoform does not play a preferential role. J. Leukoc. Biol. 81,509-519.
49. Haddad, E. K., Wu, X., Hammer, J. A., and Henkart, P. A. (2001). Defective granule exocytosis in Rab27adeficient lymphocytes from Ashen mice. J. Cell Biol. 152,835-842.
50. Haverstick, D. M., Engelhard, V. H., and Gray, L. S. (1991). Three intracellular signals for cytotoxic T lymphocyte mediated killing. Independent roles for protein kinase C, Ca2+ influx, and Ca2+ release from internal stores. J. Immunol. 146, 3306-3313.
51. Herz, J., Pardo, J., Kashkar, H., Schramm, M., Kuzmenkina, E., Bos, E., Wiegmann, K., Wallich, R., Peters, P. J., Herzig, S., Schmelzer, E., Kronke, M., Simon, M. M., and Utermohlen, O. (2009). Acid sphingomyelinase is a key regulator of cytotoxic granule secretion by primary T lymphocytes. Nat. Immunol. 10, 761-768.
52. Huse, M., Lillemeier, B. E, Kuhns, M. S., Chen, D. S., and Davis, M. M. (2006). T cells use two directionally distinct pathways for cytokine secretion. Nat. Immunol. 7, 247-255.
53. Isakov, N., and Altman, A. (2002). Protein kinase C 0 in T cell activation. Annu. Rev. Immunol. 20, 761-794.
54. Jiang, K., Zhong, B., Gilvary, D. L., Corliss, B. C, Hong-Geller, E., Wei, S., and Djeu, J. Y. (2000). Pivotal role of PI-3 kinase in regulation of cytotoxicity in natural killer cells. Nat. Immunol. 1,419-425.
55. Jiang, K., Zhong, B., Gilvary, D. L., Corliss, B. C, Vivier, E., Hong-Geller, E., Wei, S., and Djeu, J.Y. (2002). Syk regulation of phosphoinositide 3-kinase-dependent NK cell function. J. Immunol. 168, 3155-3164.
56. Karre, K., Ljunggren, H. G., Piontek, G., and Kiessling, R. (1986). Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature 319,675-678.
57. Kasibhlatla, S., Genestier, L., and Green, D. R. (1999). Regulation of Fas ligand expression during activationinduced cell death in T lymphocytes via nuclear factor KB. J. Biol. Chem. 274, 987-992.
58. Kato, H., Takeuchi, O., Sato, S., Yoneyama, M., Yamamoto, M., Matsui, K., Uematsu, S., Jung, A., Kawai, T., Ishii, K., Yamaguchi, O., Otsu, K., Tsujimura, T., Koh, C. S., Reis e Sousa, C, Matsuura, Y, Fujita, T., and Akira, S. (2006). Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 441, 101-105.
59. KEGGpathway. (2011). Natural Killer Cell Mediated Cytotoxicity -Homo sapiens. Available at: http:// www.genome.jp/kegg/pathway/hsa/ hsa04650.html
60. Kelly, J. M., Darcy, P. K., Markby, J. L, Godfrey, D. I., Takeda, K., Yagita, H., and Smyth, M. J. (2002). Induction of tumor-specific T cell memory by NK cell-mediated tumor rejection. Nat. Immunol. 3, 83-90.
61. Koebel, C. M., Vermi, W., Swann, J. B., Zerafa, N., Rodig, S. J., Old, L. J., Smyth, M. J., and Schreiber, R. D. (2007). Adaptive immunity maintains occult cancer in an equilibrium state. Nature 450, 903-907.
62. Kong, K. F., Yokosuka, T., Canonigo-Balancio, A. J., Isakov, N., Saito, T., and Altman, A. (2011). A motif in the V3 domain of the kinase PKC-0 determines its localization in the immunological synapse and functions in T cells via association with CD28. Nat. Immunol. 12, 1105-1112.
63. Konig, S., Nimtz, M., Scheiter, M., Ljunggren, H. G., Bryceson, Y. T., and Jansch, L. (2012). Kinome analysis of receptor-induced phosphorylation in human natural killer cells. PLoS ONE 7, e29672. doi:10.1371/joumal.pone.0029672
64. Kroger, N. (2011). Approaches to relapse after allogeneic stem cell transplantation. Curr. Opin. Oncol. 23,203-208.
65. Krzewski, K., Chen,X., Orange, J. S., and Stromminger, J. L. (2006). Formation of a WIP-, WASp-, actin-, and myosin IIA-containing multiprotein complex in activated NK cells and its alteration by KIR inhibitory signaling.J. Cell Biol. 173, 121-132.
66. Krzewski, K., Chen, X., and Strominger, J. L. (2008). WIP is essential for lytic granule polarization and NK cell cytotoxicity. Proc. Natl. Acad. Sci. U.S.A. 105,2568-2573.
67. Krzewski, K., and Strominger, J. L. (2008). The killer's kiss: the many functions of NK cell immunological synapses. Curr. Opin. Cell Biol. 2008, 597-605.
68. Kuhn, J. R., and Poenie, M. (2002). Dynamic polarization of the microtubule cytoskeleton during CTLmediated killing. Immunity 16, 111-121.
69. Lanier, L. L. (2008). Up on the tightrope: natural killer cell activation and inhibition. Nat. Immunol. 9,495-502.
70. Latinis, K. M., Norian, L. A., Eliason, S. L, and Koretzky, G. A. (1997). Two NFAT transcription factor binding sites participate in the regulation of CD95 (Fas) ligand expression in activated human T cells. J. Biol. Chem. 272, 31427-31434.
71. Li, C, Ge, B., Nicotra, M., Stern, J. N., Kopcow, H. D., Chen, X., and Strominger, J. L. (2008). JNK MAP kinase activation is required for MTOC and granule polarization in NKG2D-mediated NK cell cytotoxicity. Proc. Natl. Acad. Sci. U.S.A. 105, 3017-3022.
72. Liu, R. B., Engels, B., Arina, A., Schreiber, K., Hyjek, E., Schietinger, A., Binder, D. C, Butz, E., Krausz, T., Rowley, D. A., Jabri,B.,andSchreiber,H. (2012). Densely granulated murine NK cells eradicate large solid tumors. Cancer Res. 72, 1964-1974.
73. Ljunggren, H. G., and Karre, K. (1985). Host resistance directed selectively gainst H-2-deficient lymphoma variants. Analysis of the mechanism. J. Exp. Med. 162, 1745-1795.
74. Lopez-Botet, M., Bellon, T., Llano, M., Navarro, F., Garcia, P., and de Miguel, M. (2000). Paired inhibitory and triggering NK cell receptors for HLA class I molecules. Hum. Immunol. 61, 7-17.
75. Marcenaro, S., Gallo, E, Martini, S., Santoro, A., Griffiths, G., Arico, M., Moretta, L., and Pende, D. (2006). Analysis of natural killer-cell function in familial hemophagocytic lymphohistiocytosis (FHL): defective CD 107a surface expression heralds Muncl3-4 defect and discriminates between genetic subtypes of the disease. Blood 108, 2316-2323.
76. Melief, C. J. M. (2007). Immune pact with the enemy. Nature 450, 803-804.
77. Miller, J. S., Soignier, Y., Panoskaltsis-Mortari, A., McNearney, S. A., Yun, G. H., Fautsch, S. K., McKenna, D., Le, C, Defor, T. E., Burns, L. J., Orchard, P. J., Blazar, B. R., Wagner, J. E., Slungaard, A., Weisdorf, D. J., Okazaki, I. J., and McGlave, P. B. (2005). Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood 105,3051-3057.
78. Monks, C. R. E, Kupfer, H., Tamir, I., Barlow, A., and Kupfer, A. (1997). Selective modulation of protein kinase C-0 during T-cell activation. Nature 385, 83-86.
79. Moretta, A., Marcenaro, E., Parolini, S., Ferlazzo, G., and Moretta, L. (2008). NK cells at the interface between innate and adaptive immunity. Cell Death Differ. 15, 226-233.
80. Mustelin, T., Coggeshall, K. M., Isakov, N., and Altman, A. (1990). T cell antigen receptor-Mediated activation of phospholipase C requires tyrosine phosphorylation. Science 247, 1584-1587.
81. Nedellec, S., Sabourin, C, Bonneville, M., and Scotet, E. (2010). NKG2D costimulates human Vy9VS2 T cell antitumor cytotoxicity through protein kinase C9-dependent modulation of early TCR-induced calcium and transduction signals. J. Immunol. 185,55-63.
82. Nesic, D., Henderson, S., and Vukmanovic, S. (1998). Prevention of antigen-induced MTOC reorientation in cytotoxic T cells by modulation of PKC activity. Int. Immunol. 10,1741-1746.
83. Nishimura, T., Burakoff, S. J., and Herrmann, S. H. (1987). Protein kinase C required for cytotoxic T lymphocyte triggering. J. Immunol. 139, 2888-2891.
84. Orange, J., Harris, K., Andzelm, M., Valter, M., Geha, R., and Strominger, J. (2003). The mature activating natural killer cell immunologic synapse is formed in distinct stages. Proc. Natl. Acad. Sci. U.S.A. 100,14151-14156.
85. O'Rourke, A. M., and Mescher, M. F. (1992). Cytotoxic T-lymphocyte activation involves a cascade of signalling and adhesion events. Nature 358,253-255.
86. Page, K. M., Chaudhary, D., Goldman, S. J., and Kasaian, M. T. (2008). Natural killer cells from protein kinase C 0 - J - mice stimulated with interleukin-12 are deficient in production of interferon-y. J. Leukoc. Biol. 83,1267-1276.
87. Pardo, J., Balkow, S., Anel, A., and Simon, M. M. (2002). Granzymes are critically involved in NKmediated control of RMA-S tumor growth in vivo. Eur. J. Immunol. 32, 2881-2886.
88. Pardo, J., Buferne, M., Martinez-Lorenzo, M. J., Naval, J., Schmitt-Verhulst, A. M., Boyer, C, and Anel, A. (2003). Differential implication of PKC isoforms in TCR/CD3-induced Fas ligand expression and in CTL degranulation. Int. Immunol. 15, 1441-1450.
89. Pfeifhofer, C, Kofler, K., Gruber, T., Tabrizi, N.G., Lutz, C., Maly, K., Leitges, M., and Baier, G. (2003). Protien kinase C 0 affects Ca2+ mobilization and NFAT cell activation in primary mouse T cells. J. Exp. Med. 197, 1525-1535.
90. Puente, L. G., He, J. S., and Ostergaard, H. L. (2006). A novel PKC regulates ERK activation and degranulation of cytotoxic T lymphocytes: plasticity in PKC regulation of ERK. Eur. J. Immunol. 36, 1009-1018.
91. Quann, E. J., Liu, X., Altan-Bonnet, G., and Huse, M. (2011). A cascade of protein kinase C isozymes promotes cytoskeletal polarization in T cells. Nat. Immunol. 12, 647-654.
92. Reefman, E., Kay, J. G., Wood, S. M., Offenhauser, C, Brown, D. L., Roy, S., Stanley, A. C, Low, P. C, Manderson, A. P., and Stow, J. L. (2010). Cytokine secretion is distinct from secretion of cytotoxic granules in NK cells. J. Immunol. 184, 4852-4862.
93. Robertson, L. K., Mireau, L. R., and Ostergaard, H. L. (2005). A role for phosphatidylinositol 3-kinase in TCR-stimulated ERK activation leading to paxillin phosphorylation and CTL degranulation. J. Immunol. 175,8138-8145.
94. Robertson, L. K., and Ostergaard, H. L. (2011). Paxillin associates with the microtubule cytoskeleton and the immunological synapse of CTL through its leucine-aspartic acid domains and contributes to microtubule organizing center reorientation.J. Immunol. 187,5824-5833.
95. Rubnitz, J. E., Inaba, H., Ribeiro, R. C, Pounds, S., Rooney, B., Bell, T., Pui, C. H., and Leung, W (2010). NKAML: a pilot study to determine the safety and feasibility of haploidentical natural killer cell transplantation in childhood acute myeloid leukemia. J. Clin. Oncol. 28, 955-959.
96. Ruggeri, L., Mancusi, A., Burchielli, E., Aversa, E, Martelli, M. E, and Velar di, A. (2007a). Natural killer cell alloreactivity in allogeneic hematopoietic transplantation. Curr. Opin. Oncol. 19, 142-147.
97. Ruggeri, L., Mancusi, A., Capanni, M., Urbani, E., Carotti, A., Aloisi, T., Stern, M., Pende, D., Perruccio, K., Burchielli, E., Topini, F., Bianchi, E., Aversa, F., Martelli, M. F., and Velardi, A. (2007b). Donor natural killer cell allorecognition of missing self in haploidentical hematopoietic transplantation for acute myeloid leukemia: challenging its predictive value. Blood 110, 433-440.
98. Screpanti, V., Wallin, R. P. A., Ljunggren, H.G., and Grandien, A. (2001). A central role for death receptormediated apoptosis in the rejection of tumors by NK cells. J. Immunol. 167,2068-2073.
99. Secrist, J. P., Karnitz, L., and Abraham, R. T. (1991). T-cell antigen receptor ligation induces tyrosine phosphorylation of phospholipase C-yl. J. Biol. Chem. 266, 12135-12139.
100. Segovis, C. M., Schoon, R. A., Dick, C. J., Nacusi, L. P., Leibson, P. J., and Billadeau, D. D. (2009). PI3K links NKG2D signaling to a CrkL pathway involved in natural killer cell adhesion, polarity, and granule secretion. J. Immunol. 182, 6933-6942.
101. Shibuya, A., Lanier, L. L., and Phillips, J. H. (1998). Protein kinase C is involved in the regulation of both signaling and adhesion mediated by DNAX accessory molecule-1 receptor. J. Immunol. 161, 1671-1676.
102. Smyth, M. J., Kelly, J. M., Baxter, A. G., Korner, H., and Sedgwick, J. D. (1998). An essential role for tumor necrosis factor in natural killer cell-mediated tumor rejection in the peritoneum. J. Exp. Med. 188, 1611-1619.
103. Smyth, M. J., Thia, K. Y. T., Street, S. E. A., Cretney, E., Trapani, J. A., Taniguchi, M., Kawano, T., Pelikan, S. B., Crowe, N. Y, and Godfrey, D. I. (2000). Differential tumor surveillance by natural killer (NK) and NKT cells. J. Exp. Med. 191, 661-668.
104. Sorkin, L. S., Otto, M., Baldwin, W. M., Vail, E., Gillies, S. D., Handgretinger, R., Barfield, R. C, Ming Yu, H., and Yu, A. L. (2010). Anti-GD(2) with an Fc point mutation reduces complement fixation and decreases antibody-induced allodynia. Pain 149,135-142.
105. Stern, M., Ruggeri, L., Mancusi, A., Bernardo, M. E., de Angelis, C, Bucher, C, Locatelli, E, Aversa, E, and Velardi, A. (2008). Survival after T cell-depleted haploidentical stem cell transplantation is improved using the mother as donor. Blood 112,2990-2995.
106. Stinchcombe, J. C, Barral, D. C, Mules, E. H., Booth, S., Hume, A. N., Machesky, L. M., Seabra, M. C, and Griffiths, G. M. (2001a). Rab27a is required for regulated secretion in cytotoxic T lymphocytes. J. Cell Biol. 152, 825-834.
107. Stinchcombe, J. C, Bossi, G., Booth, S., and Griffiths, G. M. (2001b). The immunological synapse of CTL contains a secretory domain and membrane bridges. Immunity 15, 751-761.
108. Stinchcombe, J. C, and Griffiths, G. M. (2007). Secretory mechanisms in cell-mediated cytotoxicity. Annu. Rev. Cell Dev. Biol. 23, 495-517.
109. Sun, Z., Arendt, C. W., Ellmeier, W., Schaeffer, E. M., Sunshine, M. J., Gandhi, L., Annes, J., Petrzilka, D., Kupfer, A., Schwartzberg, P. L., and Littman, D. R. (2000). PKC-6 is required for TCR-induced NF-KB activation in mature but not in immature T lymphocytes. Nature 404, 402-407.
110. Takayama, H., and Sitkovsky, M. V. (1987). Antigen receptor-regulated exocytosis in cytotoxic T lymphocytes. J. Exp. Med. 166, 725-743.
111. Tassi, I., Cella, M., Presti, R., Colucci, A., Gilfillan, S., Littman, D. R., and Colonna, M. (2008). NK cell activating receptors require PKC9 for sustained signaling, transcriptional activation and IFN-y secretion. Blood 112,4109-4116.
112. Terme, M., Ullrich, E., Delahaye, N. F., Chaput, N., and Zitvogel, L. (2008). Natural killer cell-directed therapies: moving from unexpected results to successful strategies. Nat. Immunol. 9, 486-494.
113. Upshaw, J. L., Arneson, L. N., Schoon, R. A., Dick, C. J., Billadeau, D. D., and Leibson, P. J. (2006). NKG2D-mediated signaling requires a DAPlO-bound Grb2-Vavl intermediate and phosphatidylinositol-3-kinase in human natural killer cells. Nat. Immunol. 7, 524-532.
114. Van den Broek, M. F., Kagi, D., Zinkernagel, R. M., and Hengartner, H. (1995). Perforin dependence of natural killer cell-mediated tumor control in vivo. Eur. J. Immunol. 25, 3514-3516.
115. Velardi, A. (2008). Role of KIRs and KIR ligands in hematopoietic transplantation. Curr. Opin. Immunol. 20, 581-587.
116. Villalba, M., Bi, K., Hu, J., Altman, Y., Bushway, P., Reits, E., Neefjes, J., Baier, G., Abraham, R. T., and Altman, A. (2002). Translocation of PKC0 in T cells is mediated by a nonconventional, PI3-K- and Vavdependent pathway, but does not absolutely require phospholipase C. J. Cell Biol. 157,253-263.
117. Villalba, M., Bi, K., Rodriguez, E, Tanaka, Y., Schoenberger, S., and Altman, A. (2001a). Vavl/Racdependent actin cytoskeleton reorganization is required for lipid raft clustering in T cells.J. Cell Biol. 155, 331-338.
118. Villalba, M., Bushway, P., and Altman, A. (2001b). PKC6 mediates a selective T cell survival signal via phosphorylation of BAD. J. Immunol. 166, 5955-5963.
119. Villalba, M., Kasibhatla, S., Genestier, L., Mahboubi, A., Green, D. R., and Altman, A. (1999). Protein kinase C-0 cooperates with calcineurin to induce Fas ligand expression during activation-induced T cell death. J. Immunol. 163,5813-5819.
120. Villunger, A., Ghaffari-Tabrizi, N., Tinhofer, I., Krumbock, N., Bauer, B., Schneider, T., Kasibhatla, S., Greil, R., Baier-Bitterlich, G., Uberall, E, Green, D. R., and Baier, G. (1999). Synergistic action of protein kinase C 9 and calcineurin is sufficient for Fas ligand expression and induction of a CrmA-sensitive apoptosis pathway in Jurkat T cells. Eur. J. Immunol. 29,3549-3561.
121. Vivier, E., Tomasello, E., Baratin, M., Walzer, T., and Ugolini, S. (2008). Functions of natural killer cells. Nat. Immunol. 9,503-510.
122. Vosshenrich, C. A. J., Ranson, T., Samson, S. I., Corcuff, E., Colucci, E, Rosmaraki, E. E., and DiSanto, J. P. (2005). Roles for common cytokine receptor y-chaindependent cytokines in the generation, differentiation, and maturation of NK cell precursors and peripheral NK cells in vivo. J. Immunol. Hi, 1213-1221.
123. Vyas, Y, Maniar, H., and Dupont, B. (2002a). Visualization of signaling pathways and cortical cytoskeleton in cytolytic and noncytolytic natural killer cell immune synapses. Immunol. Rev. 189,161-178.
124. Vyas, Y. M., Maniar, H., and Dupont, B. (2002b). Differential segregation of the SRC homology 2-containing protein tyrosine phosphatase-1 within the early NK cell immune synapse distinguishes noncytolytic from cytolytic interactions. J. Immunol. 168,3150-3154.
125. Willemze, R., Rodrigues, C. A., Labopin, M., Sanz, G., Michel, G., Socie, G., Rio, B., Sirvent, A., Renaud, M., Madero, L., Mohty, M., Ferra, C, Gamier, F., Loiseau, P., Garcia, J., Lecchi, L., Kogler, G., Beguin, Y, Navarrete, C, Devos, T., Ionescu, I., Boudjedir, K., Herr, A. L., Gluckman, E., Rocha, V, and Eurocord-Netcord and Acute Leukaemia Working Party of the EBMT. (2009). KIRligand incompatibility in the graft -versus-host direction improves outcomes after umbilical cord blood transplantation for acute leukemia. Leukemia 23, 492-500.
126. Zeng, J., Cannon, J. L., Abraham, R. T., Way, M., Billadeau, D. D., Bubeck-Wardenberg, J., and Burkhardt, J. K. (2003). SLP-76 coordinates Nckdependent WASP recruitment with Vav-l/Cdc42-dependent WASP activation at the T cell-APC contact site. I Immunol. 171, 1360-1368.