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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 楊啟伸 | |
| dc.contributor.author | Yi-Chi Chen | en |
| dc.contributor.author | 陳逸奇 | zh_TW |
| dc.date.accessioned | 2021-06-13T15:17:59Z | - |
| dc.date.available | 2008-08-04 | |
| dc.date.copyright | 2008-08-04 | |
| dc.date.issued | 2008 | |
| dc.date.submitted | 2008-07-25 | |
| dc.identifier.citation | 1. Ajit, S.K. & Young, K.H. Analysis of chimeric RGS proteins in yeast for the functional evaluation of protein domains and their potential use in drug target validation. Cell Signal 17, 817-25 (2005).
2. Bansal, G., Druey, K.M. & Xie, Z. R4 RGS proteins: regulation of G-protein signaling and beyond. Pharmacol Ther 116, 473-95 (2007). 3. Barker, S.A., Wang, J., Sierra, D.A. & Ross, E.M. RGSZ1 and Ret RGS: two of several splice variants from the gene RGS20. Genomics 78, 223-9 (2001). 4. Berman, D.M., Kozasa, T. & Gilman, A.G. The GTPase-activating protein RGS4 stabilizes the transition state for nucleotide hydrolysis. J Biol Chem 271, 27209-12 (1996). 5. Beyer, C.E. et al. Regulators of G-protein signaling 4: modulation of 5-HT1A-mediated neurotransmitter release in vivo. Brain Res 1022, 214-20 (2004). 6. Bishop, G.B., Cullinan, W.E., Curran, E. & Gutstein, H.B. Abused drugs modulate RGS4 mRNA levels in rat brain: comparison between acute drug treatment and a drug challenge after chronic treatment. Neurobiol Dis 10, 334-43 (2002). 7. Burgon, P.G., Lee, W.L., Nixon, A.B., Peralta, E.G. & Casey, P.J. Phosphorylation and nuclear translocation of a regulator of G protein signaling (RGS10). J Biol Chem 276, 32828-34 (2001). 8. Chatterjee, T.K., Eapen, A.K. & Fisher, R.A. A truncated form of RGS3 negatively regulates G protein-coupled receptor stimulation of adenylyl cyclase and phosphoinositide phospholipase C. J Biol Chem 272, 15481-7 (1997). 9. Chatterjee, T.K., Liu, Z. & Fisher, R.A. Human RGS6 gene structure, complex alternative splicing, and role of N terminus and G protein gamma-subunit-like (GGL) domain in subcellular localization of RGS6 splice variants. J Biol Chem 278, 30261-71 (2003). 10. Chen, C.K. et al. Slowed recovery of rod photoresponse in mice lacking the GTPase accelerating protein RGS9-1. Nature 403, 557-60 (2000). 11. Chowdari, K.V. et al. Association and linkage analyses of RGS4 polymorphisms in schizophrenia. Hum Mol Genet 11, 1373-80 (2002). 12. Clapham, D.E. & Neer, E.J. G protein beta gamma subunits. Annu Rev Pharmacol Toxicol 37, 167-203 (1997). 13. Cunningham, M.L., Waldo, G.L., Hollinger, S., Hepler, J.R. & Harden, T.K. Protein kinase C phosphorylates RGS2 and modulates its capacity for negative regulation of Galpha 11 signaling. J Biol Chem 276, 5438-44 (2001). 14. de Vries, D.S., Bruin, M.C., Bierings, M. & Revesz, T. [Congenital amegakaryocytic thrombocytopenia: indication for allogeneic stem cell transplantation]. Ned Tijdschr Geneeskd 144, 1596-8 (2000). 15. Derrien, A. & Druey, K.M. RGS16 function is regulated by epidermal growth factor receptor-mediated tyrosine phosphorylation. J Biol Chem 276, 48532-8 (2001). 16. Derrien, A. et al. Src-mediated RGS16 tyrosine phosphorylation promotes RGS16 stability. J Biol Chem 278, 16107-16 (2003). 17. Ding, J. et al. RGS4-dependent attenuation of M4 autoreceptor function in striatal cholinergic interneurons following dopamine depletion. Nat Neurosci 9, 832-42 (2006). 18. Dohlman, H.G., Song, J., Ma, D., Courchesne, W.E. & Thorner, J. Sst2, a negative regulator of pheromone signaling in the yeast Saccharomyces cerevisiae: expression, localization, and genetic interaction and physical association with Gpa1 (the G-protein alpha subunit). Mol Cell Biol 16, 5194-209 (1996). 19. Erdely, H.A., Tamminga, C.A., Roberts, R.C. & Vogel, M.W. Regional alterations in RGS4 protein in schizophrenia. Synapse 59, 472-9 (2006). 20. Fredriksson, R., Lagerstrom, M.C., Lundin, L.G. & Schioth, H.B. The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Mol Pharmacol 63, 1256-72 (2003). 21. Fukuhara, S., Murga, C., Zohar, M., Igishi, T. & Gutkind, J.S. A novel PDZ domain containing guanine nucleotide exchange factor links heterotrimeric G proteins to Rho. J Biol Chem 274, 5868-79 (1999). 22. Geurts, M., Hermans, E. & Maloteaux, J.M. Opposite modulation of regulators of G protein signalling-2 RGS2 and RGS4 expression by dopamine receptors in the rat striatum. Neurosci Lett 333, 146-50 (2002). 23. He, W., Cowan, C.W. & Wensel, T.G. RGS9, a GTPase accelerator for phototransduction. Neuron 20, 95-102 (1998). 24. Heximer, S.P. et al. Hypertension and prolonged vasoconstrictor signaling in RGS2-deficient mice. J Clin Invest 111, 445-52 (2003). 25. Heximer, S.P. et al. G protein selectivity is a determinant of RGS2 function. J Biol Chem 274, 34253-9 (1999). 26. Hinrichs, M.V., Montecino, M., Bunster, M. & Olate, J. Mutation of the highly conserved Arg165 and Glu168 residues of human Gsalpha disrupts the alphaD-alphaE loop and enhances basal GDP/GTP exchange rate. J Cell Biochem 93, 409-17 (2004). 27. Hooks, S.B., Martemyanov, K. & Zachariou, V. A role of RGS proteins in drug addiction. Biochem Pharmacol 75, 76-84 (2008). 28. Hu, G. & Wensel, T.G. R9AP, a membrane anchor for the photoreceptor GTPase accelerating protein, RGS9-1. Proc Natl Acad Sci U S A 99, 9755-60 (2002). 29. Ingi, T. & Aoki, Y. Expression of RGS2, RGS4 and RGS7 in the developing postnatal brain. Eur J Neurosci 15, 929-36 (2002). 30. Jeong, S.W. & Ikeda, S.R. Endogenous regulator of G-protein signaling proteins modify N-type calcium channel modulation in rat sympathetic neurons. J Neurosci 20, 4489-96 (2000). 31. Jin, Y., Zhong, H., Omnaas, J.R., Neubig, R.R. & Mosberg, H.I. Structure-based design, synthesis, and pharmacologic evaluation of peptide RGS4 inhibitors. J Pept Res 63, 141-6 (2004). 32. Jin, Y., Zhong, H., Omnaas, J.R., Neubig, R.R. & Mosberg, H.I. Structure-based design, synthesis, and activity of peptide inhibitors of RGS4 GAP activity. Methods Enzymol 389, 266-77 (2004). 33. Koelle, M.R. & Horvitz, H.R. EGL-10 regulates G protein signaling in the C. elegans nervous system and shares a conserved domain with many mammalian proteins. Cell 84, 115-25 (1996). 34. Kovoor, A. et al. D2 dopamine receptors colocalize regulator of G-protein signaling 9-2 (RGS9-2) via the RGS9 DEP domain, and RGS9 knock-out mice develop dyskinesias associated with dopamine pathways. J Neurosci 25, 2157-65 (2005). 35. Kozasa, T. [Regulation of G protein-mediated signaling pathways by RGS proteins]. Seikagaku 70, 1418-22 (1998). 36. Lan, K.L. et al. A point mutation in Galphao and Galphai1 blocks interaction with regulator of G protein signaling proteins. J Biol Chem 273, 12794-7 (1998). 37. Lan, K.L., Zhong, H., Nanamori, M. & Neubig, R.R. Rapid kinetics of regulator of G-protein signaling (RGS)-mediated Galphai and Galphao deactivation. Galpha specificity of RGS4 AND RGS7. J Biol Chem 275, 33497-503 (2000). 38. Larminie, C. et al. Selective expression of regulators of G-protein signaling (RGS) in the human central nervous system. Brain Res Mol Brain Res 122, 24-34 (2004). 39. Liang, Y. et al. Identification of a novel alternative splicing variant of RGS5 mRNA in human ocular tissues. Febs J 272, 791-9 (2005). 40. Martemyanov, K.A., Hopp, J.A. & Arshavsky, V.Y. Specificity of G protein-RGS protein recognition is regulated by affinity adapters. Neuron 38, 857-62 (2003). 41. Mirnics, K., Middleton, F.A., Stanwood, G.D., Lewis, D.A. & Levitt, P. Disease-specific changes in regulator of G-protein signaling 4 (RGS4) expression in schizophrenia. Mol Psychiatry 6, 293-301 (2001). 42. Moneer, Z., Dyer, J.L. & Taylor, C.W. Nitric oxide co-ordinates the activities of the capacitative and non-capacitative Ca2+-entry pathways regulated by vasopressin. Biochem J 370, 439-48 (2003). 43. Morris, D.W. et al. Confirming RGS4 as a susceptibility gene for schizophrenia. Am J Med Genet B Neuropsychiatr Genet 125B, 50-3 (2004). 44. Mukhopadhyay, S. & Ross, E.M. Rapid GTP binding and hydrolysis by G(q) promoted by receptor and GTPase-activating proteins. Proc Natl Acad Sci U S A 96, 9539-44 (1999). 45. Neubig, R.R. Regulators of G protein signaling (RGS proteins): novel central nervous system drug targets. J Pept Res 60, 312-6 (2002). 46. Ni, Y.G. et al. Region-specific regulation of RGS4 (Regulator of G-protein-signaling protein type 4) in brain by stress and glucocorticoids: in vivo and in vitro studies. J Neurosci 19, 3674-80 (1999). 47. Pierce, K.L., Premont, R.T. & Lefkowitz, R.J. Seven-transmembrane receptors. Nat Rev Mol Cell Biol 3, 639-50 (2002). 48. Prasad, K.M. et al. Genetic polymorphisms of the RGS4 and dorsolateral prefrontal cortex morphometry among first episode schizophrenia patients. Mol Psychiatry 10, 213-9 (2005). 49. Rahman, Z. et al. Cloning and characterization of RGS9-2: a striatal-enriched alternatively spliced product of the RGS9 gene. J Neurosci 19, 2016-26 (1999). 50. Rahman, Z. et al. RGS9 modulates dopamine signaling in the basal ganglia. Neuron 38, 941-52 (2003). 51. Ramachandran, S. & Cerione, R.A. Stabilization of an intermediate activation state for transducin by a fluorescent GTP analogue. Biochemistry 43, 8778-86 (2004). 52. Riddle, E.L. et al. Polymorphisms and haplotypes of the regulator of G protein signaling-2 gene in normotensives and hypertensives. Hypertension 47, 415-20 (2006). 53. Riddle, E.L., Schwartzman, R.A., Bond, M. & Insel, P.A. Multi-tasking RGS proteins in the heart: the next therapeutic target? Circ Res 96, 401-11 (2005). 54. Saitoh, O. et al. Alternative splicing of RGS8 gene determines inhibitory function of receptor type-specific Gq signaling. Proc Natl Acad Sci U S A 99, 10138-43 (2002). 55. Saitoh, O. & Odagiri, M. RGS8 expression in developing cerebellar Purkinje cells. Biochem Biophys Res Commun 309, 836-42 (2003). 56. Saugstad, J.A., Marino, M.J., Folk, J.A., Hepler, J.R. & Conn, P.J. RGS4 inhibits signaling by group I metabotropic glutamate receptors. J Neurosci 18, 905-13 (1998). 57. Schwindinger, W.F. & Robishaw, J.D. Heterotrimeric G-protein betagamma-dimers in growth and differentiation. Oncogene 20, 1653-60 (2001). 58. Skiba, N.P., Bae, H. & Hamm, H.E. Mapping of effector binding sites of transducin alpha-subunit using G alpha t/G alpha i1 chimeras. J Biol Chem 271, 413-24 (1996). 59. Snow, B.E. et al. GTPase activating specificity of RGS12 and binding specificity of an alternatively spliced PDZ (PSD-95/Dlg/ZO-1) domain. J Biol Chem 273, 17749-55 (1998). 60. Soundararajan, M. et al. Structural diversity in the RGS domain and its interaction with heterotrimeric G protein alpha-subunits. Proc Natl Acad Sci U S A 105, 6457-62 (2008). 61. Spink, K.E., Polakis, P. & Weis, W.I. Structural basis of the Axin-adenomatous polyposis coli interaction. Embo J 19, 2270-9 (2000). 62. Tang, K.M. et al. Regulator of G-protein signaling-2 mediates vascular smooth muscle relaxation and blood pressure. Nat Med 9, 1506-12 (2003). 63. Taymans, J.M., Leysen, J.E. & Langlois, X. Striatal gene expression of RGS2 and RGS4 is specifically mediated by dopamine D1 and D2 receptors: clues for RGS2 and RGS4 functions. J Neurochem 84, 1118-27 (2003). 64. Tekumalla, P.K. et al. Elevated levels of DeltaFosB and RGS9 in striatum in Parkinson's disease. Biol Psychiatry 50, 813-6 (2001). 65. Tesmer, V.M., Kawano, T., Shankaranarayanan, A., Kozasa, T. & Tesmer, J.J. Snapshot of activated G proteins at the membrane: the Galphaq-GRK2-Gbetagamma complex. Science 310, 1686-90 (2005). 66. Thomas, E.A., Danielson, P.E. & Sutcliffe, J.G. RGS9: a regulator of G-protein signalling with specific expression in rat and mouse striatum. J Neurosci Res 52, 118-24 (1998). 67. Traynor, J.R. & Neubig, R.R. Regulators of G protein signaling & drugs of abuse. Mol Interv 5, 30-41 (2005). 68. Willard, F.S., Kimple, R.J., Kimple, A.J., Johnston, C.A. & Siderovski, D.P. Fluorescence-based assays for RGS box function. Methods Enzymol 389, 56-71 (2004). 69. Willars, G.B. Mammalian RGS proteins: multifunctional regulators of cellular signalling. Semin Cell Dev Biol 17, 363-76 (2006). 70. Williams, N.M. et al. Support for RGS4 as a susceptibility gene for schizophrenia. Biol Psychiatry 55, 192-5 (2004). 71. Wise, A. & Milligan, G. High level expression of mammalian G protein alpha subunit Gq subtypes in Escherichia coli. Biochem Soc Trans 23, 12S (1995). 72. Xie, G.X. et al. Gene structure, dual-promoters and mRNA alternative splicing of the human and mouse regulator of G protein signaling GAIP/RGS19. J Mol Biol 325, 721-32 (2003). 73. Yang, C.S., Skiba, N.P., Mazzoni, M.R. & Hamm, H.E. Conformational changes at the carboxyl terminus of Galpha occur during G protein activation. J Biol Chem 274, 2379-85 (1999). 74. Yu, J.H., Wieser, J. & Adams, T.H. The Aspergillus FlbA RGS domain protein antagonizes G protein signaling to block proliferation and allow development. Embo J 15, 5184-90 (1996). 75. Zhang, K. et al. Structure, alternative splicing, and expression of the human RGS9 gene. Gene 240, 23-34 (1999). 76. Zheng, B. et al. RGS-PX1, a GAP for GalphaS and sorting nexin in vesicular trafficking. Science 294, 1939-42 (2001). 77. Zhong, H. & Neubig, R.R. Regulator of G protein signaling proteins: novel multifunctional drug targets. J Pharmacol Exp Ther 297, 837-45 (2001). 78. Zuber, A.M., Singer, D., Penninger, J.M., Rossier, B.C. & Firsov, D. Increased renal responsiveness to vasopressin and enhanced V2 receptor signaling in RGS2-/- mice. J Am Soc Nephrol 18, 1672-8 (2007). | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/37021 | - |
| dc.description.abstract | 異三元體 G-蛋白質系統由 α、β、γ 三個次單元體所組成，參與將細胞外訊息藉由 G-蛋白質偶合受體 (G-protein-coupled receptor) 傳遞到細胞內的過程。RGS (regulator of G protein signaling) 是一種 GAP 蛋白質 (GTPase-accelerating proteins)，可和 Gα 次單元體作用並活化其本身之 GTPase 活性，在 G-protein 系統中可加速關閉訊息的傳遞。在近幾年的研究中，RGS 蛋白質的重要性逐漸提高，特別是在心血管及神經系統方面，因此許多製藥學的研究主要都是集中在影響 RGS 的 GAP 活性上，期望能降低藥物的副作用及加強其使用效率。所以需要能大量進行藥物篩選的方法來偵測 GAP 活性的效率。
本實驗中，使用 Lucifer yellow 此螢光劑標定之 RGS4-box (RGS4 之功能性區域)，即時監測其與 Gαi1 之間的作用。在所建立之 96 孔微量滴定盤分析結果顯示，Gα 處於活化態時，可觀測到約 17% 的螢光上升，確定以此螢光試劑作為篩選的方法是可產生專一且足夠的訊號。 | zh_TW |
| dc.description.abstract | Heterotimeric G-protein system consists of Gα and Gβγ subunits, and it involves in the signal transferring and amplification from GPCR (G-protein-coupled receptor) to cell inside. RGS (regulator of G protein signaling) protein functions as a GAP (GTPase-accelerating protein) by interacting and stimulating the intrinsic GTPase activity of specific Gα subunit and consequently accelerates the termination of the signal transition in G-protein system. Recently, the importance of RGS proteins is escalating, especially in the cardiovascular and nerve systems; many pharmacological studies currently focus on the GAP activity of RGS that potentially can reduce side effects or enhance drug efficiency. The need to have a high throughput drug screening method to detect GAP activity efficiencies becomes obvious.
Here, we report a method that use a fluorescent probe, lucifer yellow, modified RGS4-box (the GAP functional domain of RGS4) to real-time monitor its interaction with Gαi1 protein. Our results show that a 17% fluorescence increase upon Gα activation can be reported by this fluorescent probe and the amplitude of this signal change is practically significant enough for reagent screening purpose when it is performed in a 96-well Reader setup. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T15:17:59Z (GMT). No. of bitstreams: 1 ntu-97-R95b47215-1.pdf: 3555250 bytes, checksum: 476f54c508fea22dac3d3f8f9a0b2d61 (MD5) Previous issue date: 2008 | en |
| dc.description.tableofcontents | 中文摘要…………………………………………………………………Ⅰ
Abstract…………………………………………………………………Ⅱ 目錄………………………………………………………………………Ⅲ 圖目錄……………………………………………………………………Ⅶ 表目錄……………………………………………………………………Ⅸ 縮寫表……………………………………………………………………Ⅹ 第一章 緒論……………………………………………………………1 1.1 G-protein signal transduction…………………………………1 1.1.1 GPCR (G-protein-coupled receptor)…………………………1 1.1.2 G-protein (guanine nucleotide binding proteins)………1 1.1.3 G-protein 的下游因子 …………………………………………2 1.1.4 人體中 GPCR 訊息的傳遞 ………………………………………3 1.2 RGS (Regulator of G protein signaling) 蛋白質……………3 1.2.1 人類基因中的 RGS ………………………………………………3 1.2.2 RGS 的功能 ………………………………………………………4 1.3 藥物對 RGS 的影響…………………………………………………5 1.3.1 影響 mRNA 的表現量 ……………………………………………6 1.3.2 影響轉譯後修飾 …………………………………………………6 1.4 RGS 相關的疾病 ……………………………………………………6 1.4.1 高血壓 ……………………………………………………………7 1.4.2 精神分裂症 ………………………………………………………7 1.4.3 帕金森氏症 ………………………………………………………8 1.4.4 藥物成癮 …………………………………………………………8 1.5 RGS 藥物 ……………………………………………………………9 1.5.1 藥物的設計 ………………………………………………………9 1.5.2 成功例子…………………………………………………………10 1.6 研究動機……………………………………………………………11 第二章 材料與方法……………………………………………………12 2.1 實驗材料與藥品……………………………………………………12 2.1.1 菌種………………………………………………………………12 2.1.2 質體………………………………………………………………12 2.1.3 藥品………………………………………………………………12 2.2 實驗儀器與設備……………………………………………………12 2.2.1 核酸電泳設備……………………………………………………12 2.2.2 蛋白質電泳與轉印設備…………………………………………13 2.2.3 離心機……………………………………………………………13 2.2.4 其他………………………………………………………………13 2.3 實驗方法……………………………………………………………14 2.3.1 點突變蛋白質與其相關蛋白質之建構…………………………14 2.3.1.1 聚合酶連鎖反應 (polymerase chain reaction, PCR) …14 2.3.1.2 洋菜膠體電泳…………………………………………………15 2.3.1.3 膠體 DNA 回收 ………………………………………………16 2.3.1.4 限制酶切割及黏合……………………………………………17 2.3.1.5 質體轉型………………………………………………………17 2.3.1.6 質體 DNA 抽取 (Spin-column method)……………………18 2.3.2 以大腸桿菌 E. coli 表現重組蛋白質 ………………………18 2.3.2.1 以 E. coli BL21(DE3) 表現 RGS-box (RGS4-box、RGS9-box)………………………………………………………………………19 2.3.2.2 以 Arcticexpress RP (DE3) 表現 RGS-box (RGS4-box) 19 2.3.2.3 以 E. coli BL21(DE3) 表現 Gα (Gαi1、Gαt/i、Gαs)…19 2.3.3 重組蛋白質之純化………………………………………………20 2.3.3.1 破菌、蛋白質粗萃取…………………………………………20 2.3.3.2 超高速離心法分離蛋白質……………………………………20 2.3.3.3 金屬離子螯合層析……………………………………………21 2.3.3.4 陰離子交換法 (用於純化 Gαi1、Gαt/i)…………………22 2.3.3.5 RGS9-box refolding (用於純化以 E. coli BL21(DE3) 表現之 RGS9-box)…………………………………………………………22 2.3.4 蛋白質定量法……………………………………………………24 2.3.5 蛋白質檢定………………………………………………………24 2.3.5.1 SDS-PAGE 電泳 ………………………………………………24 2.3.5.2 蛋白質轉印及免疫染色………………………………………28 2.3.6 Lucifer yellow 標定法 ………………………………………30 2.3.7 螢光分析…………………………………………………………31 2.3.7.1 Gα 活性分析…………………………………………………31 2.3.7.2 Gα 之 GTPase 分析…………………………………………32 2.3.7.3 Lucifer yellow 螢光分析 …………………………………32 2.3.7.4 96 孔微量滴定盤螢光分析 …………………………………33 第三章 結果與討論 …………………………………………………34 3.1 螢光訊號用於篩選之可行性………………………………………34 3.1.1 純化重組蛋白質及螢光標定之蛋白質…………………………35 3.1.2 96 孔微量滴定盤之螢光掃描 …………………………………40 3.1.3 專一性分析………………………………………………………41 3.1.4 需要標定在 RGS 上的原因 ……………………………………41 3.2 RGS4-box 突變株之建構與純化 …………………………………42 3.2.1 點突變之選擇與建構……………………………………………42 3.2.2 表現系統之建立…………………………………………………44 3.2.3 RGS4-box 突變株之功能分析 …………………………………49 3.2.4 RGS4-box 突變株和 Gαi1 之結合分析………………………52 3.3 RGS4-box S131C-LY 專一性分析…………………………………54 3.3.1 Gαs-L 的建構與純化 …………………………………………54 3.3.2 RGS4-box S131C-LY 之 GAP 專一性分析 ……………………56 3.3.3 RGS4-box S131C-LY 之結合分析………………………………57 3.4 RGS4-box S131C-LY 之 96 孔微量滴定盤應用…………………58 第四章 討論與未來展望………………………………………………59 4.1 藥物篩選模式之建立………………………………………………59 4.1.1 蛋白質之功能分析………………………………………………59 4.1.2 螢光訊號之生理意義……………………………………………60 4.1.3 螢光訊號之專一性………………………………………………60 4.1.4 篩選方法之建立…………………………………………………61 4.2 結論…………………………………………………………………62 4.3 未來展望……………………………………………………………62 參考文獻…………………………………………………………………63 | |
| dc.language.iso | zh-TW | |
| dc.title | 以螢光劑修飾之 RGS 發展新的 Gα 蛋白質相關疾病之藥物篩選策略 | zh_TW |
| dc.title | Development of a new drug screening strategy using fluorescent probe modified RGS (Regulator of G protein signaling) and Gα proteins | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 96-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 陳佩燁,黃青真,楊健志,陳俊任 | |
| dc.subject.keyword | 異三元體 G-蛋白質,RGS,GAP,Lucifer yellow,螢光, | zh_TW |
| dc.subject.keyword | Heterotimeric G-protein,RGS,GAP,Lucifer yellow,fluorescence, | en |
| dc.relation.page | 71 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2008-07-25 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 微生物與生化學研究所 | zh_TW |
| 顯示於系所單位： | 微生物學科所 | |
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