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研究生:陳婉昕
研究生(外文):Wannhsin Chen
論文名稱:依賴介白質-3(IL-3)存活的血球細胞中參與其細胞存活的轉錄因子之調控
論文名稱(外文):Regulation of transcriptional factors involved in IL-3 dependent survival in hematopoietic cells
指導教授:嚴仲陽
指導教授(外文):Jeffrey Jong-Yong Yen
學位類別:博士
校院名稱:國防醫學院
系所名稱:生命科學研究所
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2001
畢業學年度:89
語文別:英文
論文頁數:125
中文關鍵詞:介白質-3細胞存活
外文關鍵詞:IL-3 dependent survival
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細胞激素 (cytokines) 在造血系統中 (hematopoiesis) 扮演極重要的角色。它可調控血球細胞由幹原細胞 (stem cells) 分化成八個不同系譜的成熟細胞,此外亦可調控這些細胞的生長與存活。細胞激素透過細胞膜上的特定受體執行作用。為了解細胞激素所調控的血球細胞存活之機制,我們利用一個老鼠的前趨 B 細胞株 (pro-B cell line: Ba/F3) 進行研究。Ba/F3 細胞必須依賴介白質-3 (IL-3) 而存活,一旦缺少介白質-3,細胞就會凋亡 (apoptosis) 而死。實驗室之前的研究發現 Ba/F3 的細胞核粹取物中,有一個蛋白質 CREB 會認得 Ces-2/E2A-HLF 的核酸結合序列 CBE,而與其結合。在本篇研究中,我們利用可活化 CREB 的藥劑 (forskolin 或 IBMX) 以及蛋白質 (PKAc、myr-Akt),證明活化的 CREB 可以透過 CBE 刺激報告質體 (reporter) 上的螢光合成酵素(Luciferase) 的轉錄 (transcription),且此刺激作用可被 dominant negative CREB 所抑制。此外 IL-3 等細胞激素亦被證明可活化 CREB。PKA 及 Akt 的活性抑制劑會抑制 CREB 的活化,且會促使細胞凋亡,活化的 PKA 及 Akt 則會保護細胞因 IL-3 移除而造成的凋亡。PKA 的保護作用進一步被證實是透過活化 CREB 而來的。此外,在穩定表現 dominant negative CREB 的細胞株中給予 IL-3 的刺激後,分析其 RNA 的表現,發現 CREB 可藉由調控 A1/BflI 基因的轉錄,參與在 IL-3 所傳遞的細胞存活訊息中,而阻止因IL-3去除造成的細胞凋亡。另外對於 Akt 參與在此抗細胞凋亡機制的研究,我們利用了二個穩定表現活化狀態的 Akt (myr-Akt) 的 Ba/F3 細胞株,以免疫螢光標定法,發現在 IL-3 移除時,Akt 可抑制粒腺體膜電位的喪失以及 cytochrome C 由粒腺體釋出至細胞質,進一步分析蛋白質的表現量,顯示Akt 可抑制 Bcl-2 家族成員中 Mcl-1 蛋白表現量之下降及 BID 蛋白活性之下降,此外也可持續刺激轉錄因子 CREB 的磷酸化,因此綜合我們對於Mcl-1啟動子的研究推測 Akt 可能藉由活化轉錄因子,調控 Bcl-2 家族成員,影響粒腺體膜完整性而達成 IL-3 誘發之抗細胞凋亡的作用。最後為了瞭解在急性淋巴球性血癌中,因染色體轉位而產生的致癌性嵌合體蛋白 E2A-HLF,在 IL-3 誘發之抗細胞凋亡中,是透過調控下游何者基因表現而達成其作用,我們構築了一個有條件的 E2A-HLF 活化質體 (EHER), 將雌性激素 (estrogen) 受體的受質結合部位,與 E2A-HLF 結合,使得 E2A-HLF可接受雌性激素的刺激而活化成具有轉錄活性的轉錄因子。我們將會把此質體送到細胞中, 在蛋白質合成抑制劑的存在下去除 IL-3時,比較有雌性激素刺激與沒有刺激的細胞中 RNA 的表現情形,希望能找到 E2A-HLF 在 IL-3 誘發的抗細胞凋亡中,受到其調控的下游基因,並進一步分析此基因在 IL-3 所傳遞的細胞存活訊息中扮演的角色。
Cytokines play an important role in hematopoiesis. They regulate the differentiation of hematopoietic stem cells into eight major lineages of mature blood cells. In addition, they also control the proliferation and survival of these cells. Cytokines act on cells through binding to their specific receptors expressed on cell membrane. In order to understand the mechanism of cytokine-dependent cell survival, we used an IL-3-dependent pro-B cell line Ba/F3 proceed the issue. Ba/F3 cells dependent on IL-3 to survive. Once withdrawal of IL-3, Ba/F3 cells are going to die by apoptosis. In our previous study on the identification of the Ces-2/E2AHLF binding protein(s) in the transcriptional regulation of apoptosis, we have found that CREB exits in the binding complex of Ces-2/E2AHLF binding element (CBE). In this study, we have demonstrated that PKA or Akt activated CREB can transactivate CBE-driven luciferase reporter activity and protect IL-3-withdrawal induced apoptosis. We have used the PKA activator forskolin or IBMX as well as active form of PKA and Akt expression constructs to activate CREB. CBE-driven luciferase reporter activity was found to be stimulated and this stimulation was blocked by dominant negative mutants of CREB. Cytokines stimulate CREB phosphorylation at serine 133. PKA and Akt inhibitors block CREB phosphorylation as well as IL-3 dependent cell survival. Whereas active form of PKA and Akt protect cells from IL-3 withdrawal induced apoptosis. The protection effect of PKA was shown to through activation of CREB. In addition, analysis of IL-3 stimulated RNA from stable lines, which were overexpressed dominant negative mutant of CREB under tet-off inducible system, we found that A1/BflI gene expression was regulated by CREB in IL-3-dependent cell survival signaling. As for the study of the role of Akt in IL-3-dependent cell survival, we have used two Ba/F3 derivative lines that were stably overexpressed constitutively active form of Akt. By the Immunofluorescence staining and flow cytometry analysis, Akt was shown to suppress the loss of mitochondria membrane potential and releasing of cytochrome c from mitochondria to cytosol upon IL-3 withdrawal. In addition, Akt also blocked the decreasing of Bcl-2 family member Mcl-1 and BID as well as phosphorylation of transcription factor CREB as IL-3 removal. Therefore, It was suggested that Akt protects IL-3-withdrawal induced cell death may act on mitochondria through regulation of transcriptional factors to control the Bcl-2 family member protein expression. Finally, the ongoing project was studying the antiapoptotic effect of E2A-HL, the chimaeric protein formed by the t (17; 19)(q22; p13) chromosomal translocation in acute lymphoblastic leukemia. In order to identify the direct downstream target gene(s) of E2A-HLF involving in IL-3-dependent antiapoptotic function, we have created a conditional activating construct of E2A-HLF by fusion the hormone-binding domain of the human estrogen receptor gene to the 3'' end of human E2A-HLF. This chimaeric protein, EHER, expresses all the time, however its transcription activity is induced by the presence of oestrogen. In the presence of the de novo protein synthesis inhibitor cyclohexamide, the mammalian estrogenic hormone: b-estradiol can induce the transcription activity of existing EHER protein. Therefore, in the presence of cyclohexamide, comparison the RNA form b-estradiol stimulating and unstimulating cells during IL-3 starvation condition, we hope to identify the direct target gene(s) of E2A-HLF involving in IL-3-dependent survival.
封面
Contents
List of Figures
List of Tables
Chinese Summery
English Summery
Chapter I: General introduction
References
Chapter II: PKA and AKT-dependent(CREB regulation in IL-3 survival signaling pathway
Abstract
Introduction
Materials and Methods
Results
Dsicussion
Figures
References
Chapter III: The role and possible mechanism of Akt/PKB in protection of IL-3-dependent cells from appptosis
Abstract
Introduction
Materials and Methods
Results
Discussion
Figures
References
ChapverIV: Identification of the direct cellular target(s) of E2A-HLF involved in apoptosis regulation
Abstract
Introduction
Materials and Methods
Results
Discussion
Figures
References
Appendixes
1. Miyajima, A., Kitamura, T., Harada, N., Yokota, T., and Arai, K. 1992. Cytokine receptor and signal transduction. Annu. Rev. Immunol. 10:295-331.
2. Yen, J.J., Yang-Yen, H.F., Huang, H.M., Hsieh, Y.C., Lee, S.F., Chao, J.R., and Lee, J.C. 1997. Molecular mechanisms of growth and death control of hematopoietic cells by cytokines. Programmed cell death. Chapter 13.
3. Nicola, N. A. 1994 Guidebook to cytokines and their receptors. Oxford University Press.
4. Thomson, A. 1991. The cytokine handbook. Chapter 1. Academic Press Limited.
5. Metcalf, D. 1989 The molecular control of cell division, differentiation commitment and maturation in haemopoietic cells. Nature 339:27-30.
6. Williams, G. T., C. A. Smith, E. Spooncer, T. M. and D.R. Taylor. 1990. Haemopoietic colony stimulating factors promote cell survival by suppressing apoptosis. Nature 343:76-79.
7. Rodriguez-Tarduchy, G., M. Collins, and A. Lopez-Rivas. 1990. Regulation of apoptosis in interleukin-3-dependent hemopoietic cells by interleukin-3 and calcium ionophores. EMBO J. 9:2997-3002.
8. Arai, Ken-ichi,Lee, K., Miyajima, A., Miyatake, S., Arai N., and Yokota, T. 1990 Cytokines: coordinators of immune and inflammatory responses. Annu. Rev. Biochem. 59:783-836.
9. Schrader, J.W. 1986. The panspecific hemopoietin of activated T lymphocytes (interleukine-3). Ann. Rev. Immunol. 4:205-30.
10. Ihle, J. N., Keller, j., Oroszlan, S., Henderson, L. E., Copeland, T. D., Fitch, F., Prystowsky, M. B., Golddwasser, E., Schrader, J. W., Palaszynski, E., Dy, M., and Lebel, B. 1983. Biologic properties of homogenous interleukin 3. 131:282-287.
11. Mire-Sluis A. and Thorpe R. 1998. Cytokines. Chpater 3: interleukine-3. Academic press.
12. Fung, M.C., Hapel, A.J., Ymer,S., et al. 1984. Molecular cloning of cDNA for murine interleukin-3. Nature. 307:233-237.
13. Otsuka, T., Miyajima, A., Brown, N., et al.1988. Isolation and characterization of an expressible cDNA encoding human IL-3. J. Immunol. 140:2288-2295.
14. Ihle, J. N., Keller, j., Henderson, L. E., Klein, F. and Palaszynski, E. 1982. Procedures for the purification of interleukin 3 to homogeneity. J. Immunol. 129:2431-2436.
15. Niemeyer, C.M., Sieff, C.A., Mathey-Prevot,B., et al. 1989. Expression of human interleukin-3 (multi-CSF) is restricted to human lymphocytes and T-cell tumor lines. Blood. 73:945-951.
16. Ymer, S., Tucker, Q. J., Sanderson, C. J., Hapel A. J., Campbell, H. D. and Young I. G. 1985. Constitutive synthesis of interleukin-3 by leukaemia cell line WEHI-3B is due to retroviral insertion near the gene. Nature. 317:255-258.
17. Leo, S. 1987. The molecular control of blood cell development. Science. 238:1374-1379.
18. Palacios, R., Henson, G., Steinmetz, M. and McKearn, J. P. 1984. Interleukin-3 supports growth of mouse pre-B-cell clones in vitro. Nature. 309:126-131.
19. Palacios, R., and Steinmetz, M. 1985. IL3-dependent mouse clones that express B-220 surface antigen, contain Ig genes in germ-line configuration, and generate B lymphocytes in vivo. Cell. 41:727-734.
20. Rennick, D., Jackson, J., Moulds, C., Lee, F. and Yang, G. 1989. IL-3 and stromal cell-derived factor synergistically stimulate the growth of pre-B cell lines cloned from long-term lymphoid bone marrow cultures. J. Immunol. 142:161-166.
21. Kitamura, T., N. Sato, K. Arai, and A. Miyajima. 1991. Expression cloning of the human IL3 receptor cDNA reveals a shared b subunit for the human IL-3 and GM-CSF receptors. Cell. 66:1165-1174.
22. Hayashida, K., T. Kitamura, D. M. gorman, K.-I. Arai, T. Yokota, and A. Miyajima.1990. Molecular cloning of a second subunit of the receptor for human granulocyte-macrophage colony-stimulating factor (GM-CSF): reconstitution of a high-affinity GM-CSF receptor. Proc. Natl. Acad. Sci. USA. 87:9655-9659.
23. Bagley, C.J., Woodcock, J.Mfactor., Stomski, F.C., and Lopez, A.F. 1997. The structural and functional basis of cytokine receptor activation: lessons from the common b subunit of the granulocyte-macrophage colony-stimulating factor, interleukin-3 (IL-3), and IL-5 receptors. Blood. 89:1471-1482.
24. Stomski, F.C., Sun, Q., Bagley, C.J., Woodcock, J., Goodall, G., Andrews, R.K., Berndt, M.C. and Lopez, A.F. 1996. Human interleukin-3 (IL-3) induces disulfide-linked IL-3 receptor a- and b-chain heterodimerization, which is required for receptor activation but not high-affinity binding. Mol. Cell. Biol.16: 3035-3046.
25. Sato, N., Sakamaki, K., Terada, N. Arai, K.-I., and Miyajima, A. 1993. Signal transduction by the high-affinity GM-CSF receptor: two distinct cytoplasmic regions of the common b subunit responsible for different signaling. EMBO. J. 12: 4181-4189.
26. Sakamaki, K., Miyajima, I., Kitamura, T. and Miyajima, A. 1992. Critical cytoplasmic domains of the common bsubunit of the human GM-CSF, IL-3 and IL-5 receptors for growth signal transduction and tyrosine phosphorylation. EMBO. J. 11:3541-3549
27. Jucker, M., and Feldman, R. A. 1996. Molecular aspects of myeloid stem cell development. Page:67-75. Springer press.
28. Thompson, C. B. 1996. A fate worse than death. Nature. 382:492-493.
29. Rathmell J. C. and Thompson, C. B. 1999. The central effectors of cell death in the immune system. Annu. Rev. Immunol. 17: 781-828.
30. Ellis, H. M. and Horvitz, R. 1986. Genetic control of programmed cell death in the nematode C. elegans. Cell. 44: 817-829.
31. Ellis, R. E. and Horvitz, R. 1991. Two C. elegans genes control the programmed deaths of specific cells in the pharynx. Development.112: 591-603.
32. Ellis, R. E. 1992. Negative regulators of programmed cell death. Current opinion in genetics and development. 2:635-641.
33. Hunot, S. and Flavell, R. A. 2001. Death of a monopoly? Science. 292: 865-867.
34. Joza, N., Susin, S. A., Daugas, E., Stanford, W. L., Cho, S. K., Li, C.Y.J., Sasaki, T., Elia, A. J., Cheng, H.-Y. M., Ravagnan, L., Ferri, K. F., Zamzami, N., Wakeham, A., Yoshida, H., Kong, Y-Y., Mak, T.W., Zuniga-Pflucker, J. C., Kroemer, G., and Penninger, J. M. 2001. Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death. Nature. 410:549-554.
35. Chao, D. T. and Korsmeyer, S. J. 1998. Bcl-2 family: regulators of cell death. Annu. Rev. Immunol. 16: 395-419.
36. Metzstein, M. M., Hengartner, M. O., Tsung, N., Ellis, R. E., and Horvitz, H. R. 1996. Transcriptional regulator of programmed cell death encoded by Caenorhabditis elegans gene ces-2. Nature. 382:545-547.
37. Inaba, T., Inukai, T., Yoshihara, T., Seyschab, H., Laken, S. J., Kastan, M. B. and Look, A. T. 1996. Reversal of apoptosis by the leukaemia-associated E2A-HLF chimaeric transcription factor. Nature. 382: 541-544.
38. Kuribara, R., Kinoshita, T., Miyajima, A., Shinjyo, T., Yoshihara, T., Inukai, T., Ozawa, K., Look, A. T., and Inaba, T. 1999. Two distinct interleukin-3-mediated signal pathways, Ras-NFIL3 (E4BP4) and Bcl-XL, regulate the survival of murine Pro-B lymphocytes. Mol. Cell. Biol. 19: 2754-2762.
39. Ikushima, S., Inukai, T., Inaba, T., Nimer, S. D., Cleveland, J.L., and Look, A. T. 1997. Pivotal role for the NFIL3/E4BP4 transcription factor in interleukin 3-mediated survival of pro-B lymphocytes. Proc. Natl. Aci. USA. 94:2609-2614.
40. Inukai, T., Inoue, A., Kurosawa, H., Goi, K., Shinjyo, T., Ozawa, K., Mao, M., Inaba, T., and Look, A. T. 1999. SLUG, a ces-1-related Zinc finger transcription factor gene with antiapoptotic activity, is a downstream target of E2A-HLF oncoprotein. Mol. Cell. 4: 343-352.
41. Walsh, D. A., Perkins, J. P., and Krebs, E. G. 1968. An adenosine 3'', 5''-monophosphate-dependent protein kinase from rabbit skeletal muscle. J. Biol. Chemi. 243: 3763-3774.
42. Wang, L., Sunahara, R. K., Krumins, A., Perkins, G., Crochiere, M. L., Mackey, M., Bell, S., Ellisman, M. H., and Taylor, S. S. 2001. Cloning and mitochondrial localization of full-length D-AKAP2, a protein kinase A anchoring protein. Proc. Natl. Aci. USA. 98: 3220-3225.
43. Corbin, J. D., Sugden, P. H., West, L., Flockhart, D. A., Lincoln,T. M., and McCarthy, D. 1978. Studies on the properties and mode of action of the purified regulatory subunit of bovine heart adenosine 3'': 5''-monophosphate-dependent protein kinase. J. Biol. Chemi. 253: 3997-4003.
44. Kennelly, P. J., and Krebs E. G. 1991. Consensus sequences as substrate specificity determinants for protein kinases and protein phosphotases. The journal of Biol. Chemi. 266:15555-15558.
45. Berkowitz, L. A. and Gilman M. Z. 1990. Two distinct forms of active transcription factor CREB (cAMP response element binding protein). Proc. Natl. Aci. USA. 87:5258-5262.
46. Harada, H., Becknell, B., Wilm, M., Mann, M., Huang, L. J.-S., Taylor. S. S., Scott, J. D., and Korsmeyer, S. J. 1999. Phosphorylation and inactivation of BAD by mitochondria-anchored protein kinase A. Mol. Cell. 3: 413-422.
47. Lowell, B. B. 1996.Slimming with a leaner enzyme. Nature. 382:585-586.
48. Cummings, D. E., Brandon, E. P., Planas, J. V., Motamed, K. Idzerda, R. L., and Mcknight, G. S. 1996. Genetically lean mice result from targeted disruption of the RIIb subunit of protein kinase A. Nature. 382:622-626.
49. Uhler, M. D., Chrivia, J. C. and McKnight, G. S. 1986. Evidence for a second isoform of the catalytic subunit of cAMP-dependent protein kinase. J. Biol. Chemi. 261: 15360-15363.
50. Beebe, S. J. Oyen, O., Sanberg, M., Froysa, A., Hansson, M. and Jahnsen, T. 1990. Molecular cloning of a tissue-specific protein kinase (Cγ) from human testis-representing a third isoform for the catalytic subunit of cAMP-dependent protein kinase. Mol. Endocri. 4: 465-475.
51. Montminy, M. R. and Bilezikjian, L. M. 1987. Binding of a nuclear protein to the cyclic-AMP response element of somatostatin gene. Nature. 328:174-178.
52. Hoefeler, J. P., Meryer, T. E., Yun, Y., Jameson, J. L. and Habener, J. F. 1988. Cyclic AMP-responsive DNA-binding protein: structure based on a cloned placental cDNA. Science. 242:1430-1433.
53. Shaywitz, A. J., and Greenberg, M. E. 1999 CREB: A stimulus-induced transcription factor activated by a diverse array of extracellular signals. Annu. Rev. Biochem. 68: 821-861.
54. Gonzalez, G. A.,and Montminy M. R. 1989. Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at Serine 133. Cell. 59: 675-680.
55. Parker, D., Ferreri, K. NakaJima, T. Lamorte, V. J., Evans, R., Koerber, S. C., Hoeger, C., and Montiminy, M. R. 1996. Phosphorylation of CREB at Ser-133 induces complex formation with CREB-binding protein via a direct mechanism. Mol. Cell. Biol. 16:694-703.
56. Sun, P., Enslen, H., Myung, P. S. and Maurer, R. A. 1994. Differential activation of CREB by Ca2+/ calmodulin-dependent protein kinase type II and type IV involves phosphorylation of a site that negatively regulates activity. Genes and Development. 8: 2527-2539.
57. Iordanov, M., Bender, K., Ade, T., Schmid, W., Sachsenmaier C., Engel, K. Gaestel, M., Rahmsdorf, H. J., and Herrlich, P. 1997. CREB is activated by UVC through a p38/HOG-1-dependent protein kinase. The EMBO J. 16:1009-1022.
58. Du, K., and Montminy, M. 1998. CREB is a regulatory target for the protein kinae AKT/PKB. J. of Biol. Chemi. 273: 32377-32379.
59. Tan, Y., Rouse, J., Zhang, Aihua, Z., Cariati, S., Cohen, P., and Comb, M. J. 1996. FGF and stress regulate CREB and ATF-1 via a pathway involving p38 MAP kinase and MAPKAP kinase-2. EMBO. J.15: 4629-4642.
60. Deak, M., Clifton, A. D., Lucocq, J.M. and Alessi, D. R. 1998. Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediated activation of CREB. EMBO. J. 17: 4426-4441.
61. Chen, W., Yu, Y-L., Lee, S-F., Chiang, Yun-J., Chao, J-R., Huang, J-H., Chiong, J-H, Huang, C-J, Lai, M-Z, Yang-Yen, H-F., and Yen, J. J.-Y. 2001. CREB is one component of the binding complex of the Ces-2/E2A-HLF binding element and is an integral part of the IL-3 survival signal. Mol. Cell. Biol. 14: 4636-4646.
62. Barton, K., Muthusamy,N. Chanyangam, M., Fischer, Clendenin, C., and Leiden, J. M. 1996. Defective thymocyte proliferation and IL-2 production in transgenic mice expressing a dominant-negative form of CREB. Nature. 379: 81-85.
63. Rudolph, D., Tafuri, A., Gass, P., Hammerling, G., Arnold, B., and Schutz, G. 1998. Impaired fetal T cell development and perinatal lethality in mice lacking the cAMP response element binding protein. Proc. Nat. Acad. Sci. USA. 95:4481-4486.
64. Bonni, A., Brunet, A., West, A. E., Datta, R., Takasu, M. A., and Greenberg, M. E. 1999. Cell Survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and independent mechanisms. Science. 286:1358-1365.
65. Finkbeiner, S. 2000. CREB couples neurotrophin signals to survival messages. Nature. 25: 11-14.
66. Yamamoto, K. K., Gonzalez, G. A., Biggs III, W. H., and Montminy, M. R.1988. Phosphorylation-induced binding and transcription efficacy of nuclear factor CREB. Nature. 334:494-498.
67. Dwarki, V. J., Montminy, M. R., and Verma, I. M. 1990. Both the basic region and the ''leucine zipper'' domain of the cyclic AMP response element binding (CREB) protein are essential for transcriptional activation. EMBO. J. 9: 225-232.
68. Montminy, M. R. Sevarino, K. A. Wagner, J. A., Mandel, G., and Goodman, R. H. 1986. Identification of a cyclic-AMP-responsive element within the rat somatostatin gene. Proc.Natl. Aci. USA. 83: 6682-6686.
69. Shepard, A. R., Zang, W., and Eberhardt, N. L. 1994. Two CGTCA motifs and a GHF1/Pit1 binding site mediate cAMP-dependent protein kinase A regulation of human growth hormone gene expression in rat anterior pituitary GC cells. J. Bio. Chemi. 269: 1804-1814
70. Ginty, D.D., Bonni, A., and Greenberg, M. E. 1994. Nerve growth factor activates a Ras-dependent protein kinase that stimulates c-fos transcription via phosphorylation of CREB. Cell. 77: 713-725.
71. Sakamoto, K. M., Fraser, J. K., Lee, H.-J. J., Lehman, E., and Gasson, J. C. 1994. Granulocyte-Macrophage colony-stimulating factor and interleukin-3 signaling pathways converge on the CREB-binding site in the human egr-1 promoter. Mol. Cell. Biol. 14: 5975-5985.
72. Wilson, B. E., Mochon, E., and Boxer, L. M. 1996. Induction of bcl-2 Expression by phosphorylated CREB proteins during B-cell activation and rescue from apoptosis. Mol. Cell. Biol. 16:5546-5556.
73. Riccio A., Ahn, S., Davenport, C. M., Blendy, J. A., and Ginty, D. D. 1999. Mediation by a CREB family transcription factor of NGF-dependent survival of sympathetic neurons. Science.286: 2358-2361.
74. Hemmings, B. A. 1997. AKT signaling- linking membrane events to life and death decisions. Science. 275: 628-630
75. Andjelkovice, M., Aless, D. R., Merier, R., Fernandez, A., Lamb, N. J. C. Frech, M., Cron, P., Cohen, P., Lucocq, J. M., and Hemmings, B. A. 1997. Role of Translocation in the activation and function of protein kinase B. J. Biol. Chemi. 272: 31515-31524.
76. Downd, J. 1998. Lipid-regulated kinase: some common themes at last. Science. 279:673-674.
77. Yano, S., Tokumitsu, H. and Soderling, T. R. 1998. Calcium promote cell survival through CaM-K kinase activation of the protein-kinase-B pathway. Nature. 396: 584-587.
78. Kulik, G., Kilppel, A., and Weber, M. J. 1997. Antiapoptotic signalling by the insulin-like growth factor I receptor, phosphatidylinositol 3-kinase, and AKT. Mol. Cell. Biol. 17:1595-1606.
79. Wang, J.-M., Chao, J-R., Chen, W., Kuo, M.-L., Yen, J. J.-Y., and Yang-Yen, H.-F. 1999. The antiapoptotic gene mcl-1 is up-regulated by the phosphatidylinositol 3-kinase/Akt signaling pathway through a transcription factor complex containing CREB. Mol. Cell. Biol. 19: 6195-6206.
80. Cross, D. A. E., Alessi, D. R., Cohen, D., Andjelkovich, M., Hemmings, B. A. 1995. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature. 378: 785-789.
81. Datta. S. R., Dudek, H., Tao, X., Masters, S., Fu, H., Gotoh, Y., and Greenberg, M. E. 1997. AKT phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Mol. Cell. Biol. 91: 231-241.
82. Cardone, M. H., Roy, N., Stennicke, H. R., Salvesen, G. S., Franke, T. F., Stanbridge, E., Frisch, S., and Reed, J. C. 1998. Regulation of cell death protease caspase-9 by phosphorylation. Science. 282:1318-1321.
83. Kim, A. H., Khursigara, G., Sun, X., Franke. T. F., and Chao, M. V. 2001. AKT phosphorylates and negatively regulates apoptosis signal-regulating kinase 1. Mol. Cell. Biol. 21: 893-901.
84. Brunet, A., Bonni, A., Zigmond, M. J., Lin, M. Z., Juo, P., Hu, L.S., Anderson, M. J., Arden, K. C., Blenis, J., and Greenberg, M. E. 1999. AKT promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell. 96: 857-868.
85. Lee, S.-F., Huang H.-M., Chao, J.-R., Lin, S., Yang-Yen H.-F., and Yen, J. J.-Y. 1999. Cytokine receptor common b chain as a potential activator of cytokine withdrawal-induced apoptosis. Mol. Cell. Biol. 19:7399-7409.
86. Chao J.-R., Wang, J.-M., Lee, S.-F., Peng, H.-W., Lin, Y.-H., Chou, C.-H., Li, J.-C., Huang, H.-M., Chou, C.-K., Kuo, M-L., Yen, J. J.-Y., and Yang-Yen, H.-F. 1998. Mcl-1 is an immediate-early gene activated by the Granulocyte-Macrophage colony-stimulating factor (GM-CSF) signaling pathway and is one component of the GM-CSF viability response. Mol. Cell. Biol. 18: 4883-4898.
87. Kinoshita, T., Shirouzu, M., Kamiya, A., Hashimoto, K., Yokoyama, S., and Miyajima, A. 1997. Raf/MAPK and rapamycin-sensitive pathways mediate the anti-apoptotic function of p21Ras in IL-3dependent hematopoietic cells. Oncogene. 15:619-627.
88. Kinoshita, T., Yokota, T., Arai, K.-i., and Miyajima, A. 1995. Suppression of apoptotic death hematopietic cells by signaling through the IL-3/GM-CSF receptors. The EMBO. J. 14: 266-275.
89. Terada, K., Kaziro, Y., and Satoh, T. 1995. Ras is not required for the Interleukin 3-induced proliferation of a mouse pro-B cell line, Ba/F3. J. Biol. Chemi. 270: 27880-27886.
90. Ohta, T., Kinoshita, T., Naito, M., Nozaki, T., Masutani, M., Tsuruo, T. and Miyajima, A. 1997. Requirement of the Caspase-3/CPP32 protease cascade for apoptotic death following cytokine deprivation in hematopoietic cells. J. Biol. Chemi. 272: 23111-23116.
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1. 盧建旭,1995,「公共企業精神:公共企業家的角色與批判」,空大行政學報,第四期,頁135-136,1995。
2. 蔣基萍,2000,「剖析警察與社會的互動關係」,警學叢刊,5月,第30卷,第6期,頁95-118。
3. 李銘崇,1999,「政府網際服務網─政府機關網路服務單一窗口」,研考雙月刊,12月,第23卷,第6期,頁10-17。
4. 魏啟林,1999,「全面推展電子化政府邁向資訊行政新紀元」,研考雙月刊,10月,第23卷,第5期,頁3-11。
5. 葉毓蘭、李政峰,1998,「警民共治的新警政─社區改善治安的策略聯盟模式」,社區發展季刊,第82期,頁-23。
6. 楊朝祥,1999,「邁向數位時代的智慧型政府」,研考雙月刊,2月,第23卷,第1期,頁3-9。
7. 曾淑芬、張良銘,1998,「醫療資訊網站之內容分析及使用者調查」,醫療資訊雜誌,12月,第八期,頁54-72。
8. 黃朝盟、趙美慧,2000,「政府網站管理應避免的十大錯誤」,研考雙月刊,6月,第24卷,第3期,頁41-47。
9. 李湧清,2000,「論當代民主社會中警察的角色與功能」,警學叢刊,5月,第30卷,第6期,頁79-93。
10. 江偉平,1999,「推動政府機關服務上網加強電子化政府便民服務」,研考雙月刊,10月,第23卷,第5期,頁12-16。
11. 朱愛群,1998,「論警察機關三個競值組織典範─刑案偵破、犯罪預防及為民服務」,中央警察大學學報,第33期,頁69-82。