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研究生:魏志璋
研究生(外文):Chih-Chang Wei
論文名稱:利用肝癌細胞株Hep3B探討ZAK導致細胞凋零死亡的結構區
論文名稱(外文):Mapping apoptotic domain of ZAK on cultured hepatoma cell line, Hep3B
指導教授:楊肇基楊肇基引用關係李天翎
指導教授(外文):Jaw-Ji Yang Ph. D.Tien-Ling Lee Ph. D.
學位類別:碩士
校院名稱:中山醫學院
系所名稱:口腔醫學研究所
學門:醫藥衛生學門
學類:牙醫學類
論文種類:學術論文
論文出版年:2001
畢業學年度:89
語文別:中文
論文頁數:78
中文關鍵詞:ZAK細胞凋零蛋白質激酶leucine zipperSAMJNK/SAPK
外文關鍵詞:ZAKapoptosisprotein kinaseleucine zipperSAMJNK/SAPK
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摘要
Mixed-lineage kinase (MLK) 家族的蛋白質激酶是最近才被發現的蛋白質,這類蛋白質在其kinase domain後具有一個或二個leucine zipper domains,並可特異性的活化JNK/SAPK的活性,屬於MAPK cascade中的MAPKKK。ZAK為2000年Liu Te-Chung等人所發表的一個新穎的蛋白質激酶,依其在kinase domain的結構和功能並具有leucine zipper的特性,因而被歸類為MLK家族的新成員,除可活化JNK/SAPK外,ZAK也可活化NF-κB的活性,且對肝癌細胞株Hep3B具有細胞毒性,而這個現象經證實是透過apoptosis所造成的。
本次實驗乃是希望藉由自C端作連續不同片段缺失的突變型ZAK蛋白質,找出其引起apoptosis的結構區域為何。結果發現一旦ZAK自C端向N端缺失到不具完全的SAM domain時,則將喪失活化JNK/SAPK的活性,且細胞毒性也大大減少,而其在細胞內的分佈也由原來分佈於細胞質中變成可出現在細胞核內,雖然將SAM整個移除其又可恢復活化JNK/SAPK的能力,並仍可出現在核中,不過在細胞毒性的表現上已明顯降低,這些結果顯示ZAK上的SAM domain可能影響ZAK在細胞中的分佈,而此現象與其誘發Hep3B細胞發生apoptosis可能有關。
關鍵詞:ZAK、apoptosis、protein kinase、leucine zipper、SAM、JNK/SAPK

Abstract
The protein kinase of mixed-lineage kinase (MLK) was recently identified. The kinase domain of MLK family proteins belongs to MAPKKK of MAPK cascade, which is followed by one or two leucine zipper domains and specifically activate JNK/SAPK. A novel protein kinase ZAK was published by Liu et al. lately. Due to its possessing of a domain with structure and function similar to that of kinase domain and characteristic of containing leucine zipper, it was classified as a new member of MLK family. In addition to JNK/SAPK, ZAK also activates NF-κB. Moreover it has been proven that ZAK induces cytotoxicity of Hep3B hepatoma cell line via apoptosis.
This study was aimed at mapping the apoptotic domain of ZAK by analyzing ZAK proteins which are a series of sequential deletions strating from C terminals. Surprisingly, when the portion of ZAK from C terminal to SAM domain were largely deleted but it still retains partial SAM domain, it no longer activates JNK/SAPK and decreases its cytotoxicity noticeablely. And the mutated ZAKs were observed in both cytoplasms and nuclei, albeit it was only found in cytoplasms originally. Mutated ZAKs regain its capability to activate JNK/SAPK while remain to be located in nuclei and have a decreasing cytotoxicity until the SAM domain was completely removed. These results suggested that SAM domain of ZAK might be responsible for or artibute to localization and this might be a mechanism for how ZAK induce apoptosis of Hep3B cell line.

目錄
縮寫表………………………………………………………………Ⅰ
圖次……………………………………………………………………Ⅱ
表次……………………………………………………………………Ⅲ
中文摘要…………………………………………………………………1
英文摘要…………………………………………………………………2
前言………………………………………………………………………4
壹、文獻探討……………………………………………………………6
一、細胞的訊號傳遞……..………………………………………6
二、蛋白質激酶…………………………………………………..8
三、磷酸化和去磷酸化……………………………………..……10
四、蛋白質對蛋白質相互作用的重要性……………………….12
五、MAPK family的重要性……………………………………16
六、與stress-respond有關的JNK pathway…………………….19
七、JNK所參與的細胞凋零死亡……………………………….21
八、一個新的mixed-lineage kinase, ZAK的發現……………….22
九、研究動機與目的…………………………………….……….25
貳、實驗材料……………………………………………………….…27
一、菌種 (Bacteria Strain) 及質體 (Plasmid) ………….…….27
二、細胞株來源及培養條件………………………………………….27
三、藥品試劑……………………………………………..………27
四、實驗儀器……………………………………………………..30
五、溶液、緩衝液(buffer)及培養液(medium)之配製……………32
參、實驗方法………………………………………………………….35
一、Transfection…………………………………………………35
二、細胞存活率試驗………………………………………….36
三、北方點墨法 (Northern Blot)………………………………36
四、DNA質體的製備…………………………………38
1. 聚合酶鏈鎖反應 (PCR) ………………………………38
2. 限制酶的處理…………………………………………39
3. 接合酶的處理…………………………………………40
4. Competent Cell的製備…………………………………40
5. Transformation試驗…………………………………41
五、西方點墨法 (Western Blot)………………………………41
六、觀察ZAK於細胞內之分佈情形 (Localization)……………42
七、胞外 (in vitro) JNK蛋白質激酶之活性試驗………………43
肆、實驗結果………………………………………………………….45
一、觀察ZAK對細胞造成死亡的效果………………………45
二、五種不同壓力刺激處理後ZAK RNA表達的變化………45
三、質體DNA pEGFPC1ZAK 3’端連續不同片段缺失的建構46
四、不同片段缺失的ZAK對Hep3B細胞存活的影響………46
五、利用GFP螢光蛋白標示出ZAK蛋白質於細胞內之分佈情形……………………………………………………………47
六、不同片段缺失的ZAK對JNK活性的影響………………48
伍、討論……………………………………………………………….49
陸、結論………………………………………………………….55
柒、參考文獻………………………………………………………….68

參考文獻
Aelst, L.V., and Souza-Schorey, C.D. (1997). Rho GTPases and signaling networks. Genes Dev. 11: 2295-2322
Aplin, A.E., Howe, A.K., and Juliano, RL (1999). Cell adhesion molecules, signal transduction and cell growth. Curr. Opin. Cell Biol. 11: 737-744
Aravind, L., Dixit, V.M., and Koonin, E.V. (2001) Apoptotic molecular machinery: vastly increased complexity in vertebrates revealed by genome comparisons. Science 291: 1279-1284
Ashkenazi A., and Dixit, V.M. (1998) Death receptors: signaling and modulation Science 281: 1305-1308
Bartkiewicz, M., Houghton, and Baron, R. (1999). Leucine zipper-mediated homodimerization of the adaptor protein c-Cbl. J. Biol. Chem. 274: 30887-30895
Blume-Jensen, P., and Hunter, T. (2001) Oncogenic kinases signalling. Nature. 411: 355-365
Brunet, A., Roux, D., Lenormand, P., Dowd, S., Keyse, S., and Pouyssgur, J. (1999) Nuclear translocation of p42/p44 mitogen-activated protein kinase is required for growth factor-induced gene expression and cell cycle entry. EMBO J. 18: 664-674
Budihardjo I., Oliver, H., Lutter, M., Luo, X., and Wang, X. (1999) Biochemical, pathways of caspase activation during apoptosis. Annu. Rev. Cell Dev. Biol. 15: 269-290
Burack, W.R., and Shaw, A.S. (2000). Signal transduction: hanging on a scaffold. Curr. Opin. Cell Biol. 12:211-216
Burridge, K., and Chrzanowska-Wodnicka, M. (1996). Focal adhesions, contractility, and signaling. Annu. Rev. Cell Dev. Biol. 12: 463-519
Chi, S.W., Ayed, A., and Arrowsmith, C.H. (1999). Solution structure of a conserved C-terminal domain of p73 with structural homology to the SAM domain. EMBO J. 16: 4438-4445
Chinnaiyan, A.M., Orth, K., O’Rourke, K., Duan, H., Poirier, G.G., and Dixit V.M. (1996). Molecular Ordering of the cell death pathway. J. Biol. Chem. 271: 4573-4576
Cotter, T.G., and Al-Rubeai, M. (1995). Cell death (apoptosis) in cell culture systems. Tib Tech. 13: 150-155
Critchley, D.R. (2000) Focal adhesions-the cytoskeletal connection. Curr. Opin. Cell Biol. 12: 133-139
Davis, R.J. (2000). Signal transduction by JNK group of MAP kinase. Cell. 103: 239-252
Delhase, M., Hayakawa, M., Chen, Y., and Karin, M. (1999) Positive and negative regulation of IκB kinase activity through IKKβ subunit phosphorylation. Science 284: 309-313
Denu, J.M., and Dixon, J.E. (1998). Protein tyrosine phosphatases: mechanisms of catalysis and regulation. Curr. Opin. Chem. Biol. 2: 633-641
Dèrijard, B., Hibi, M., Wu, IH, Barrett, T., Su, B., Deng, T., Karin, M., and Davis R.J. (1994). JNK1: A protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell. 76: 1025-1037
Desagher, S., and Martinou, J.C. (2000). Mitochondria as the central control point of apoptosis. Trends Cell Biol. 10: 369-377
Dhanasekaran N (1998). Cell signaling: an overview. Oncogene. 17: 1329-1330
Dhanasekaran N and Reddy E.P. (1998). Signaling by dual spectificity kinases. Oncogene. 17: 1447-1455
Dragovich, T, Rudin, C.M., and Thompson, C.B. (1998) Signal transduction pathways that regulate cell survival and cell death. Oncogene.17: 3207-3213
Erred B., and Ge, Q.Y. (1996) Feedback regilation of map kinase sugnal pathways. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 351: 143-148
Fan, G., Merritt, S.E., Kortenjann, M., Shae, P.E., and Holzman L.B. (1996) Dual leucine zipper-bearing kinase (DLK) activates p46SAPK and p38mapk but not ERK2 J. Biol. Chem. 271: 24788-24793
Ferrell, J.E., Jr. (2000). What do scaffold proteins really do? http://www.stke.org/cgi/content/full/OC_sigtrans;2000/52/pe1
Fu, H., Subramanian, R.R., and Masters, S.C. (2000). 14-3-3 proteins: Structure, function, and regulation. Annu. Rev. Pharmacol. Toxicol. 40: 617-647
Fukuda, K., Gotoch, Y., and Nishida, E. (1997). Interaction of MAP kinase with MAP kinase kinase: its possible role in the control of nucleocytoplasmic transport of MAP kinase. EMBO J. 16: 1901-1908
Garrington, T.P., and Johnson, G.L. (1999).Organization and regulation of mitogen-activated protein kinase signaling pathways. Curr. Opin. Cell Biol. 11: 211-218
Giancott, F.G., and Ruoslahti, E. (1999). Integrin signaling. Science. 285: 1028-1032
Goillot, E., Raingeaud, J., Ranger, A., Tepper, R.I., Davis, R.J., Harlow, E., and Sanchez, I. (1997). Mitogen-activated protein kinase-mediated Fas apoptosic signaling pathway. Proc. Natl. Acad. Sci. 94: 3302-3307
Görlich, D., and Kutay, U. (1999). Transport between the cell nucleus and the cytoplasm. Annu. Rev. Cell Dev. Biol. 15: 607-660
Gotoh, I., Adachi, M., and Nishida, E. (2001). Idenfification and characterization of a novel MAP kinase kinase kinase, MLTK. J. Biol. Chem. 276: 4276-4286
Gross, A., McDonnell, J.M., and Korsmeyer, S.J. (1999) Bcl-2 family members and the mitochondria in apoptosis. Genes Dev. 13: 1899-1911
Gutkind, J.S. (1998). Cell growth control by G protein-couple receptors: from signal transduction to signal integration. Oncogene. 17: 1331-1342
Haldar, S., Jena, N., and Croce, C.M. (1995) Inactivation of Bcl-2 by phosphorylation. Proc. Natl. Acad. Sci. USA. 92: 4507-4511
Hanks, SK, and Hunter, T. (1995) Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification. FASEB J. 9: 576-596
Hehner, S.P., Hofmann, T.G., Ushmorov, A., Dienz, O., Leung, I.W., Lassam, N., Scheidereit, C., Droge, W., and Achmitz, M.L. (2000) Mixed-lineage kinase 3 delivers CD3/CD28-derived signals into the IκB kinase complex. Mol. Cell. Biol. 20: 2556-2568
Holzman, L.B., Merritt, S.E., and Fan, G. (1994) Identification, molecular cloning, and characterization of dual leucine zipper bearing kinase J. Biol. Chem. 269: 30808-30817
Hood, J.K., and Silver, P.A. (1999). In or out? Regulating nuclear transport. Curr. Opin. Cell Biol. 11: 241-247
Huber, H. (2000). Organization of complex situations in the immune system. EMBO reports. 1: 304-312
Hunter, T. (1995). Protein kinases and phosphatases: the yin and yang of protein phosphorylation and signaling. Cell. 85: 225-236
Hunter, T. (1997) Oncoprotein networks. Cell. 88: 333-346
Hunter, T. (2000) Signaling─2000 and beyond. Cell. 100: 113-127
Holzman, L.B., Merritt, S.E., and Fan, G. (1994). Identification, molecular cloning, and characterization of dual leucine zipper bearing kinase. J. Biol. Chem. 269: 30808-30817
Ikeda A., Masaki M., Kozutsumi Y., Oka S., and Kawasaki T. (2001). Identification and characterization of functional domains in a mixed lineage kinase LZK. FEBS Letters. 488(3): 190-195
Ingber, D.E. (1997) Tensegrity: The architectural basis of cellular mechanotrasduction. Annu. Rev. Physiol. 59: 575-599
Ip, Y.T. and Davis, R.J. (1998). Signal transduction by the c-Jun N-terminal kinase(JNK)-from inflammation to development. Curr. Opin. Cell Biol. 10: 205-219
Israël, A. (2000). The IKK complex: an integrator of all signals that activate NF-κB? Trends Cell Biol. 10: 129-133
Israels, L.G., and Israels, E.D. (1999). Apoptosis. Stem Cell. 17: 306-313
Ito, M., Yoshioka, K., Akechi, M., Yamashita, S., Takamatsu, N., Sugiyama, K., Hibi, M., Nakabeppu, Y., Shiba, T., and Yamamoto, K.I. (1999). JSAP1, a novel Jun N-terminal protein kinase(JNK)-binding protein that functions as a scaffold factor in the JNK signaling pathway. Mol. Cell. Biol. 19: 7539-7548
Jordan, J.D., Landau, E.M., and Iyengar, R. (2000). Signaling networks: The origins of cellular multitasking. Cell. 103: 193-200
Jun, T., Gjoerup, O., and Roberts, T.M. (1999) Tangled webs: Evidence of cross-talk between c-Raf-1 and Akt. http://www.stke.org/cgi/content/full/OC_sigtrans;1999/13/pe1
Kallal, L., and Benovic, J.L. (2000) Using green fluorescent proteins to study G-protein-coupled receptor localization and trafficking. TiPS. 21: 175-180
Karin, M., and Hunter, T. (1995) Transcriptional control by protein phosphorylation: signal transmission from the cell surface to the nucleus. Curr. Biol. 5: 747-757
Karin, M., Liu, Z.G., and Zandi, E. (1997) AP-1 function and regulation. Curr. Opin. Cell Biol. 9: 240-246
Karin, M., and Ben-Neriah, Y. (2000). Phosphorylation meets ubiquitination: The control of NF-κB activity. Annu. Rev. Immu. 18: 621-663
Karin, M., Liu, Z.G., and Zandi, E. (1997). AP-1 function and regulation. Curr. Opin. Cell Biol. 9: 240-246
Keyse, S.M. (2000). Protein phosphatases and the regulation of mitogen-activated protein kinase signaling. Curr. Opin. Cell Biol. 12: 186-192
Kholodenko, B.N., Hoek, J.B., and Westerhoff, H.V. (2000) Why cytoplasmic signalling proteins should be recruited to cell membranes. Trends Cell Biol. 10: 173-178
Kumar C.C. (1998). Signaling by integrin receptors. Oncogene. 17: 1365-1373
Kyriakis J.M., and Avruch, J. (1990) pp54 microtubule-associated protein 2 kinase J. Biol. Cell 265: 17355-17363.
Leung, I. WL, and Lassam, N. (1998). Dimerization via tandem leucine zippers is essential for the activation of the mitogen-activated protein kinase kinase kinase, MLK-3. J. Biol. Chem. 273: 32408-32415
Levchenko, A., Bruck, J., and Sternberg, P.W. (2000). Scaffold proteins may biphasically affect the levels of mitogen-activated protein kinase signaling and reduce its threshold properties. Proc. Natl. Acad. Sci. U. S. A. 97: 5818-5823
Liu, T.C., Huang, C.J., Chu, Y.C., Wei, C.C., Chou, C.C., Chou, M.Y., Chou, C.K., and Yang, J.J. (2000) Cloning and expression of ZAK, a mixed lineage kinase-like protein containing a leucine-zipper and a sterile-alpha motif. Biochem. Biophys. Rese. Commun.. 274: 811-812
Ludwig, S., Hoffmeyer, A., Goebeler, M., Kilian, K., Häfner, H., Neufeld, B., Han, J., and Rapp, U.R. (1998). The stress inducer arsenite activates mitogen-activated protein kinases extracellular signal-regulated kinases 1 and 2 via a MAPK kinase 6/p38-dependent pathway. J. Biol. Chem. 273: 1917-1922
Mackay, D.J, and Hall, A. (1998). Rho GTPases. J. Biol. Chem. 273: 20685-20688
Marius (1998). From Src homology domains to other signaling modules: proposal of the “protein recognition code”. Oncogene. 17: 1469-1474
Marshall, C. (1999) How do small GTPase signal transduction pathways regulate cell cycle entry? Curr. Opin. Cell Biol. 11: 732-736
Mattaj, I.W., and Englmeier, L. (1998). Nucleocytoplasmic transport: the soluble phase. Annu. Rev. Biochem. 67: 265-306
May, G.H., Allen, K.E., Clark, W., and Funk, M. (1998). Analysis of the Interaction between c-Jun and c-Jun N-terminal kinase in vivo. J. Biol. Chem. 273: 33429-33435
Maundrell, K., Antonsson, B., Magnenat, E., Camps, M., Muda, M., Chabert, C., Gillieron, C., Boschert, U., Vial-Knecht, E., Martinou, J.C., and Arkinstall, S. (1997). Bcl-2 undergoes phosphorylation by c-Jun N-terminal kinase/stress-activated protein kinases in the presence of the constitutively active GTP-binding protein Rac1. J. Biol. Chem. 272: 25238-25242
Merritt, S.E., Mata, M., Nihalan, D., Zhu, C., Hu, X., and Holzman, L.B. (1999). The mixed lineage kinase DLK utilizes MKK7 and not MKK4 as substrate. J. Biol. Chem. 274: 10195-10202
Minden, A., Lin, A., Clart, F-X., Abo, A., and Karin, M. (1995) Selective actication of the JNK signaling cascade and c-jun transcription activity by the small GTPases Rac and Cdc42Hs. Cell. 81: 1147-1157
Nagata, S. (1997). Apoptosis by death factor. Cell. 88: 355-365
Naor, Z., Benard, O., and Seger. R. (2000). Activation of MAPK cascades by G-protein-coupled receptors: the case of gonadotropin-releasing hormone receptor. TEM. 11: 91-99
Nebreda, A.R., and Porras, A. (2000) p38 MAP kinases: beyond the stress response. TIBS. 25: 257-260
Nihalani, D., Merritt, S., and Holzman, L.B. (2000). Identification of structural and functional domain in mixed lineage kinase dual leucine zipper-bearing kinase required for complex formation and stress-activated protein kinase activation. J. Biol. Chem. 275: 7273-7279
Nihalani, D., Meyer, D., Pajni, S., and Holzman, L.B. (2001). Mixed lineage kinase-dependent JNK activation is governed by interactions of scaffold protein JIP with MAPK module components. EMBO J. 20: 3447-3458
Pawson, T., and Scott, I.D. (1997). Signaling through scaffold, anchoring, and adaptor proteins. Science. 278: 2075-2080
Pawson, T., and Nash, P. (2000). Protein-protein interactions define specificity in signal transduction. Genes Dev. 14: 1027-1047
Phelan, D.R., Price, G., Liu, Y.F., and Dorow, D.S. (2001). Activated JNK phosphorylates the C-terminal domain of MLK2 that is required for MLK2-induced apoptosis. J. Biol. Chem. 276: 10801-10810
Ponting CP. (1995). SAM: a novel motif in yeast sterile and Dorsophila polyhomeotic proteins. Protein Sci. 4: 1928-1930
Price, L.S., Leng, J., Schwartz, M.A., and Bokoch, G.M. (1998). Activation of Rac and cdc42 by mediates cell spreading. Mol. Biol. Cell 9: 1863-1871
Rana, A., Gallo, K., Godowski, P., Hirai, S.I., Ohno, S., Zon, L., Kyriakis, J.M., and Avruch, J. (1996) Tmixed-lineage kinase SPRK phosphorylates and activates the stress-activated protein kinase activator, SEK-1 J.Biol. Chem. 271: 19025-19028
Rhoads, R.E. (1999). Signal transduction pathways that regulate eukaryotic protein synthesis. J.Biol. Chem. 274: 30337-30340
Robinson, M.J., and Cobb, M.H. (1997). Mitogen-activated protein kinase pathways. Curr. Opin. Cell Biol. 9: 180-186 Robinson, M.J., and Cobb, M.H. (1997). Mitogen-activated protein kinase pathways. Curr. Opin. Cell Biol. 9: 180-186
Roovers, K., and Assoian, R.K. (2000). Integrating the MAP kinase signal into the G1 phase cell cycle machinery. BioEssays. 22: 818-826
Saikumar, P., Dong, Z., Mikhailo, V., Dentin, M., Weinberg, J., and Venkatachalam, M.A. (1999) Apoptosis: definition, mechanisms, and releveance to diease. Am. J. Med 107: 489-506.
Schaeffer, H.J., and Weber, M.J. (1999) Mitogen-activated protein kinases: specific messages from ubiquitous messengers. Mol. Cell. Biol. 19: 2435-2444
Schillace, Robynn V., Scott, J.D. (1999). Organization of kinases, phosphatases, and receptor signaling complexes. J. Clin. Invest. 103(6): 761-765
Schmidt, A., Caron, E., and Hall, A. (2001). Lipopolysaccharide- induced activation of β2-Integrin function in macrophages requires Irak kinase activity, p38 mitogen-activated protein kinase, and the Rap1 GTPase. Mol. Cell. Biol. 23:438-448
Schwartz, M.A., and Baron, V. (1999). Interactions between mitogenic stimuli, or, a thousand and one connections. Curr. Opin. Cell Biol. 11: 197-202
Schwartz, M.A., and Shattil, S.J. (2000) Signaling networks linking integrins and Rho family GTPase. TIBS. 25: 388-391
Srivastava, R.K., Mi, Q.S., Hardwick, J.M., and Longo, D.L.(1999) Delection of the loop region of Bcl-2 completely blocks paclitaxel-induced apoptosis. Proc. Natl. Acad. Sci. USA. 96: 3775-3780
Subauste, M.C., Herrath, M.V., Benard, V., Chamberlain, C.F, Chung, T.H., Chu, K., Bokoch, G.M., and Hahn, K.M. (2000). Rho family proteins modulate rapid apoptosis induced by cytotoxic T lymphocytes and Fas. J. Biol. Chem. 275: 9725-9733
Sugiura, R., Toda, T., Dhut, S., Shuntoh, H., and Kuno, T. (1999).The MAPK kinase Pek1 acts as a phosphorylation-dependent molecular switch. Nature. 399: 479-483
Symons, M., and Settleman, J. (2000). Rho family GTPases: more than simple switches. Trends. Cell Biol. 10: 415-419
Tanaka, S., and Hanafusa, H. (1998) Guanine-necleotide exchange protein C3G activates JNK1 by a Ras-independent mechanism. J. Biol. Chem. 273: 1281-1284
Tapon, N., Nagata, K.I., Lamarche, N., and Hall, A. (1998). A new Rac target POSH is an SH3-containing scaffold protein involved in JNK and NF-κB signaling pathway. EMBO J. 17: 1395-1404]
Taylos, S.S., Radzio-Andzelm, E., and Hunter, T. (1995) How do protein kinases discriminate between serine/threonine and tyrosine? Structural insights from the receptor protein-tyrosine kinase. FASEB J. 9: 1255-1266
Teramoto, H., Coso, O.A., Miyata, H., Igishi, T., Miki, T., and Gutkind, J.S. (1996). Signaling from the small GTP-binding proteins Rac1 and Cdc42 to the c-Jun N-terminal kinase/Stress-activated protein kinase pathway. J. Biol. Chem. 271: 27225-27288
Thanos CD, and Bowie JU (1999) P53 family members p63 and p73 are SAM domain-containing proteins. Protein Sci. 8: 1708-1710
Thanos, C.D., Goodwill, K.E., and Bowie, J.U. (1999). Oligomeric structure of the human EphB2 receptor SAM domain. Science. 283: 833-836
Thanos, C.C., Faham, S., Goodwill, K.E., Cascio, D., Phillips, M., and Bowie J.U. (1999). Monomeric structure of the human EphB2 sterile α motif domain. J. Biol. Chem. 274: 37301-37306
Thyornberry N.A., and Lazebnik, Y. (1998) Caspases: enemis within. Science 281: 1312-1316
Tournier, C., Hess, P., Yang, D.D., Xu, J., Turner, T.K., Nimnual, A., Bar-Sagi, D., Jones, S.N., Flavell, R.A., and Davis, R.J. (2000) Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway. Science 288: 870-874
Tsujimoto, Y., and Shimizu, S. (2000) Bcl-2 family: life-or-death switch. FEBS L. 466: 6-10
Vacratsis, P.O., and Gallo, M.A. (2000). Zipper- mediated oligomerization of the mixed lineage kinase SPRK/MLK-3 is not required for its activation by the GTPase cdc 42 but is necessary for its avtivation of the JNK pathway. J. Biol. Chem. 275: 27893-27900
Waskiewicz, A.J., and Cooper, J.A. (1995). Mitogen and stress response pathway: MAP kinase cascades and phosphatase regulation in mammals and yeast. Curr. Opin. Cell Biol. 7: 798-805
Whitmarsh, A.J., Cavanagh, J., Tournier, C., Yasuda, J., and Davis, R.J. (1998). A mammalian scaffold complex that selectively mediated MAP kinase activated. Science. 281: 1671-1674
Whitmarsh, A.J. and Davis, R.J. (1999). Signal transduction by MAP kinases: Regulation by phosphorylation-dependent switches. http://www.stke.org/chi/conteny/full/OC_sigtrans;1999/1/pe1
Widmann, C., Gibson, S., and Johnson, G.L. (1998). Caspase- dependent cleavage of signaling proteins during apoptosis. J. Biol. Chem. 273: 7141-7147
Widmann, C., Gibson, S., Jarpe, M.B. and Johnson G.L. (1999). Mitogen-activated protein kinase: conservation of a tree-kinases module from yeast to human. Physiol. Rev. 79: 143-180
Xing, H., Zhang, S., Weinheimer, C., Kovacs, A., and Muslin, A.J. (2000). 14-3-3 proteins block apoptosis and differentially regulate MAPK cascades. EMBO J. 19: 349-358
Xu, Z., Maroney, A.C., Dobrzanski, P., Kukekov, N.V., and Greene, L.A. (2001). The MLK family mediates c-Jun N-terminal kinase activation in neuronal apoptosis. Mol. Cell. Biol. 21: 4713-4724
Yamamoto, K., Ichijo, H., and Korsmeyer, S.J. (1999) Bcl-2 is phosphorylated and inactivated by an ASK/Jun N-terminal protein kinase pathway normally activated at G2/M. Mol. Cell. Biol. 19: 8469-8478
Yasuda J., Whitmarsh AJ., Cavanagh J., Sharma M., and Davis, R.J. (1999). The JIP group of mitogen-activated protein kinase scaffold protein. Mol. Cell. Biol. 19: 7245-7254
Zacharias, D.A., Baird, G.S., and Tsien, R.Y. (2000). Recent advances in technology for measuring and manipulating cell signals. Curr. Opin. Cell Biol. 10: 416-421
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