乙型和丙型肝炎病毒蛋白对蛋白酪氨酸激酶信号转导的影响
张忠东, 成军, 钟彦伟, 中国人民解放军第302医院传染病研究所基因治疗研究中心、全军病毒性肝炎防治研究重点实验室 北京市 100039
张树林,西安交通大学第一医院传染科 陕西省西安市 710061
项目负责人: 成军,100039, 北京市西四环中路100号,中国人民解放军第302医院传染病研究所基因治疗研究中心、全军病毒性肝炎防治研究重点实验室.cj@genetheray.com.cn
电话:010-66933392 传真:010-63801283
收稿日期:2003-01-11 接受日期:2003-02-16
, 百拇医药
张忠东,成军,钟彦伟, 张树林. 乙型和丙型肝炎病毒蛋白对蛋白酪氨酸激酶信号转导的影响. 世界华人消化杂志 2003;11(8):1261-1264
Weinmaster GA, Middlemas DS, Hunter T. A major site of tyrosinephosphorylation within the SH2 domain of
Fujinami sarcoma virus P130 gag-fps is notrequired for protein-tyrosine kinase activity or transforming potential.J
Virol 1988;62:2016-2025
5 Karin M, Hunter T. Transcriptional control by proteinphosphorylation: signal transmission from the cell surface to
, 百拇医药
the nucleus. Curr Biol 1995;5:747-757
6 Schindler C, Shuai K, Prezioso VR, Darnell JE Jr.Interferon-dependent tyrosine phosphorylation of a latent
cytoplasmic transcription factor. Science 1992;257:809-813
7 Van der Geer P, Hunter T, Lindberg RA. Receptor protein-tyrosinekinases and their signal transduction pathways.
Annu Rev Cell Biol 1994;10:251-337
, 百拇医药
8 Brabyn CJ, Kleine LP. EGF causes hyperproliferation and apoptosisin T51B cells: involvement of high and low affinity
EGFR binding sites. Cell Signal 1995;7:139-150
9 Darnell JE Jr, Kerr IM, Stark GR. Jak-STAT pathways andtranscriptional activation in response to IFNs and
other extracellular signaling proteins.Science 1994;264:1415-1421
10 Leonard WJ, O'shea JJ. Jaks and STATs: biological implications.Annu Rev Immunol 1998;16:293-322
, 百拇医药
11 Stahl N, Farruggella TJ, Boulton TG, Zhong Z, Darnell JE Jr,Yancopoulos GD. Choice of STATs and other
substrates specified by modulartyrosine-based motifs in cytokine receptors. Science 1995;267:1349-1353
12 Schlessinger J, Ullrich A. Growth factor signaling by receptortyrosine kinases. Neuron 1992;9:383-391
13 Ihle JN. The Janus protein tyrosine kinases in hematopoieticcytokine signaling. Semin Immunol 1995;7:247-254
, 百拇医药
14 Kessler DS, Veals SA, Fu XY, Levy DE. Interferon-alpha regulatesnuclear translocation and DNA-binding affinity of
ISGF3, a multimeric transcriptionalactivator. Genes Dev 1990;4:1753-1765
15 Daley GQ, Baltimore D. Transformation of an interleukin 3-dependenthematopoietic cell line by the chronic
myelogenous leukemia-specific P210 bcr/ablprotein. Proc Natl Acad Sci USA 1988;85:9312-9316
, 百拇医药
16 Cambier N, Chopra R, Strasser A, Metcalf D, Elefanty AG. BCR-ABLactivates pathways mediating cytokine
independence and protection against apoptosis inmurine hematopoietic cells in a dose dependent manner.
Oncogene 1998;16:335-348
17 Ito Y, Kawakatsu H, Takeda T, Sakon M, Nagano H, Sakai T, MiyoshiE, Noda K, Tsujimoto M, Wakasa K, Monden
M, Matsuura N. Activation of c-Src geneproduct in hepatocellular carcinoma is highly correlated with the indicesof
, 百拇医药
early stage phenotype. J Hepatol 2001;35:68-73
18 Ito Y, Takeda T, Sakon M, Tsujimoto M, Higashiyama S, Noda K,Miyoshi E, Monden M, Matsuura N. Expression and
clinical significance of erb-B receptorfamily in hepatocellular carcinoma. Br J Cancer 2001;84:1377-1383
19 Masaki T, Okada M, Tokuda M, Shiratori Y, Hatase O, Shirai M,Nishioka M, Omata M. Reduced C-terminal Src kinase
, 百拇医药
(Csk) activities in hepatocellularcarcinoma. Hepatology 1999;29:379-384
20 Benn J, Schneider RJ. Hepatitis B virus HBx protein activatesRas-GTP complex formation and establishes a Ras, Raf
MAP kinase signaling cascade. Proc NatlAcad Sci USA 1994;91:10350-10354
21 Benn J, Su F, Doria M, Schneider RJ. Hepatitis B virus HBx proteininduces transcription factor AP-1 by activation
, 百拇医药
of extracellular signal-regulated and c-JunN-terminal mitogen-activated protein kinases. J Virol 1996;70:4978-4985
22 Haviv I, Shamay M, Doitsh G, Shaul Y. Hepatitis B virus pX targetsTFIIB in transcription coactivation. Mol Cell
Biol 1998;18:1562-1569
23 Haviv I, Vaizel D, Shaul Y. pX, the HBV-encoded coactivator,interacts with components of the transcription machinery
, http://www.100md.com
and stimulates transcription in a TAF-independentmanner. EMBO J 1996;15:3413-3420
24 Klein NP, Schneider RJ. Activation of Src family kinases byhepatitis B virus HBx protein and coupled signaling to Ras.
Mol Cell Biol 1997;17:6427-6436
25 Klein NP, Bouchard MJ, Wang LH, Kobarg C, Schneider RJ. Src kinasesinvolved in hepatitis B virus replication. EMBO
J 1999;18:5019-5027
, 百拇医药
26 Natoli G, Avantaggiati ML, Chirillo P, Puri PL, Ianni A, Balsano C,Levrero M. Ras- and raf-dependent activation of c-
jun transcriptional activity by thehepatitis B virus transactivator pX. Oncogene 1994;9:2837-2843
27 Dandri M, Schirmacher P, Rogler CE. Woodchuck hepatitis virus Xprotein is present in chronically infected woodchuck
liver and woodchuck hepatocellularcarcinomas which are permissive for viral replication. J Virol 1996;70:5246-5254
, http://www.100md.com
28 Wang HD, Yuh CH, Dang CV, Johnson DL. The hepatitis B virus Xprotein increases the cellular level of TATA-binding
protein which mediates transactivation ofRNA polymerase III genes. Mol Cell Biol 1995;15:6720-6728
29 Chirillo P, Falco M, Puri PL, Artini M, Balsano C, Levrero M,Natoli G. Hepatitis B virus pX activates NF-kB-dependent
transcription through a Raf-independentpathway. J Virol 1996;70:641-646
, 百拇医药
30 Su F, Schneider RJ. HBV HBx protein activates transcription factorNF-kBby acting on multiple cytoplasmic inhibitors
of rel-related proteins. J Virol 1996;70:4558-4566
31 Su F, Schneider RJ. Hepatitis B virus HBx protein sensitizes cellsto apoptotic killing by tumor necrosis factor alpha.
Proc Natl Acad Sci USA 1997;94:8744-8749
32 Cong YS, Yao YL, Yang WM, Kuzhandaivelu N, Seto E. The hepatitis Bvirus X-associated protein, XAP3, is a protein
, 百拇医药
kinase C-binding protein. J Biol Chem 1997;272:16482-16489
33 Cross JC, Wen P, Rutter WJ. Transactivation by hepatitis B virus Xprotein is promiscuous and dependent on
mitogen activated cellular serine/threoninekinases. Proc Natl Acad Sci USA 1993;90:8078-8082
34 Doria M, Klein N, Lucito R, Schneider RJ. The hepatitis B virus HBxprotein is a dual specificity cytoplasmic activator of
, http://www.100md.com
Ras and nuclear activator of transcriptionfactors. EMBO J 1995;14:4747-4757
35 Wang HD, Trivedi A, Johnson DL. Hepatitis B virus X protein inducesRNA polymerase III-dependent gene transcription
and increases cellular TATA-binding proteinby activating the Ras signaling pathway. Mol Cell Biol 1997;17:6838-6846
36 Benn J, Schneider RJ. Hepatitis B virus HBx protein deregulatescell cycle checkpoint controls. Proc Natl Acad Sci
, 百拇医药
USA 1995;92:11215-11219
37 Miller DM, Rahill BM, Boss JM, Lairmore MD, Durbin JE, Waldman JW,Sedmak DD. Human cytomegalovirus inhibits
major histocompatibility complex class IIexpression by disruption of the Jak/Stat pathway. J Exp Med
1998;187:675-683
38 Velazquez L, Fellous M, Stark GR, Pellegrini S. A protein tyrosinekinase in the interferon alpha/beta signaling
, http://www.100md.com
pathway. Cell 1992;70:313-322
39 Heim MH, Moradpour D, Blum HE. Expression of hepatitis C virusproteins inhibits signal transduction through the jak-
STAT pathway. J Virol 1999;73:8469-8475
40 Kato N, Yoshida H, Kioko Ono-Nita S, Kato J, Goto T, Otsuka M, LanK, Matsushima K, Shiratori Y, Omata M. Activation
of intracellular signaling by hepatitis Band C viruses: C-viral core is the most potent signal inducer. Hepatology
2000;32:405-412
41 Yoshida T, Hanada T, Tokuhisa T, Kosai K, Sata M, Kohara M,Yoshimura A. Activation of STAT3 by the hepatitis C
virus core protein leads to cellulartransformation. J Exp Med 2002;5:641-653, 百拇医药( 张忠东, 成 军, 钟彦伟, 张树林)
张树林,西安交通大学第一医院传染科 陕西省西安市 710061
项目负责人: 成军,100039, 北京市西四环中路100号,中国人民解放军第302医院传染病研究所基因治疗研究中心、全军病毒性肝炎防治研究重点实验室.cj@genetheray.com.cn
电话:010-66933392 传真:010-63801283
收稿日期:2003-01-11 接受日期:2003-02-16
, 百拇医药
张忠东,成军,钟彦伟, 张树林. 乙型和丙型肝炎病毒蛋白对蛋白酪氨酸激酶信号转导的影响. 世界华人消化杂志 2003;11(8):1261-1264
Weinmaster GA, Middlemas DS, Hunter T. A major site of tyrosinephosphorylation within the SH2 domain of
Fujinami sarcoma virus P130 gag-fps is notrequired for protein-tyrosine kinase activity or transforming potential.J
Virol 1988;62:2016-2025
5 Karin M, Hunter T. Transcriptional control by proteinphosphorylation: signal transmission from the cell surface to
, 百拇医药
the nucleus. Curr Biol 1995;5:747-757
6 Schindler C, Shuai K, Prezioso VR, Darnell JE Jr.Interferon-dependent tyrosine phosphorylation of a latent
cytoplasmic transcription factor. Science 1992;257:809-813
7 Van der Geer P, Hunter T, Lindberg RA. Receptor protein-tyrosinekinases and their signal transduction pathways.
Annu Rev Cell Biol 1994;10:251-337
, 百拇医药
8 Brabyn CJ, Kleine LP. EGF causes hyperproliferation and apoptosisin T51B cells: involvement of high and low affinity
EGFR binding sites. Cell Signal 1995;7:139-150
9 Darnell JE Jr, Kerr IM, Stark GR. Jak-STAT pathways andtranscriptional activation in response to IFNs and
other extracellular signaling proteins.Science 1994;264:1415-1421
10 Leonard WJ, O'shea JJ. Jaks and STATs: biological implications.Annu Rev Immunol 1998;16:293-322
, 百拇医药
11 Stahl N, Farruggella TJ, Boulton TG, Zhong Z, Darnell JE Jr,Yancopoulos GD. Choice of STATs and other
substrates specified by modulartyrosine-based motifs in cytokine receptors. Science 1995;267:1349-1353
12 Schlessinger J, Ullrich A. Growth factor signaling by receptortyrosine kinases. Neuron 1992;9:383-391
13 Ihle JN. The Janus protein tyrosine kinases in hematopoieticcytokine signaling. Semin Immunol 1995;7:247-254
, 百拇医药
14 Kessler DS, Veals SA, Fu XY, Levy DE. Interferon-alpha regulatesnuclear translocation and DNA-binding affinity of
ISGF3, a multimeric transcriptionalactivator. Genes Dev 1990;4:1753-1765
15 Daley GQ, Baltimore D. Transformation of an interleukin 3-dependenthematopoietic cell line by the chronic
myelogenous leukemia-specific P210 bcr/ablprotein. Proc Natl Acad Sci USA 1988;85:9312-9316
, 百拇医药
16 Cambier N, Chopra R, Strasser A, Metcalf D, Elefanty AG. BCR-ABLactivates pathways mediating cytokine
independence and protection against apoptosis inmurine hematopoietic cells in a dose dependent manner.
Oncogene 1998;16:335-348
17 Ito Y, Kawakatsu H, Takeda T, Sakon M, Nagano H, Sakai T, MiyoshiE, Noda K, Tsujimoto M, Wakasa K, Monden
M, Matsuura N. Activation of c-Src geneproduct in hepatocellular carcinoma is highly correlated with the indicesof
, 百拇医药
early stage phenotype. J Hepatol 2001;35:68-73
18 Ito Y, Takeda T, Sakon M, Tsujimoto M, Higashiyama S, Noda K,Miyoshi E, Monden M, Matsuura N. Expression and
clinical significance of erb-B receptorfamily in hepatocellular carcinoma. Br J Cancer 2001;84:1377-1383
19 Masaki T, Okada M, Tokuda M, Shiratori Y, Hatase O, Shirai M,Nishioka M, Omata M. Reduced C-terminal Src kinase
, 百拇医药
(Csk) activities in hepatocellularcarcinoma. Hepatology 1999;29:379-384
20 Benn J, Schneider RJ. Hepatitis B virus HBx protein activatesRas-GTP complex formation and establishes a Ras, Raf
MAP kinase signaling cascade. Proc NatlAcad Sci USA 1994;91:10350-10354
21 Benn J, Su F, Doria M, Schneider RJ. Hepatitis B virus HBx proteininduces transcription factor AP-1 by activation
, 百拇医药
of extracellular signal-regulated and c-JunN-terminal mitogen-activated protein kinases. J Virol 1996;70:4978-4985
22 Haviv I, Shamay M, Doitsh G, Shaul Y. Hepatitis B virus pX targetsTFIIB in transcription coactivation. Mol Cell
Biol 1998;18:1562-1569
23 Haviv I, Vaizel D, Shaul Y. pX, the HBV-encoded coactivator,interacts with components of the transcription machinery
, http://www.100md.com
and stimulates transcription in a TAF-independentmanner. EMBO J 1996;15:3413-3420
24 Klein NP, Schneider RJ. Activation of Src family kinases byhepatitis B virus HBx protein and coupled signaling to Ras.
Mol Cell Biol 1997;17:6427-6436
25 Klein NP, Bouchard MJ, Wang LH, Kobarg C, Schneider RJ. Src kinasesinvolved in hepatitis B virus replication. EMBO
J 1999;18:5019-5027
, 百拇医药
26 Natoli G, Avantaggiati ML, Chirillo P, Puri PL, Ianni A, Balsano C,Levrero M. Ras- and raf-dependent activation of c-
jun transcriptional activity by thehepatitis B virus transactivator pX. Oncogene 1994;9:2837-2843
27 Dandri M, Schirmacher P, Rogler CE. Woodchuck hepatitis virus Xprotein is present in chronically infected woodchuck
liver and woodchuck hepatocellularcarcinomas which are permissive for viral replication. J Virol 1996;70:5246-5254
, http://www.100md.com
28 Wang HD, Yuh CH, Dang CV, Johnson DL. The hepatitis B virus Xprotein increases the cellular level of TATA-binding
protein which mediates transactivation ofRNA polymerase III genes. Mol Cell Biol 1995;15:6720-6728
29 Chirillo P, Falco M, Puri PL, Artini M, Balsano C, Levrero M,Natoli G. Hepatitis B virus pX activates NF-kB-dependent
transcription through a Raf-independentpathway. J Virol 1996;70:641-646
, 百拇医药
30 Su F, Schneider RJ. HBV HBx protein activates transcription factorNF-kBby acting on multiple cytoplasmic inhibitors
of rel-related proteins. J Virol 1996;70:4558-4566
31 Su F, Schneider RJ. Hepatitis B virus HBx protein sensitizes cellsto apoptotic killing by tumor necrosis factor alpha.
Proc Natl Acad Sci USA 1997;94:8744-8749
32 Cong YS, Yao YL, Yang WM, Kuzhandaivelu N, Seto E. The hepatitis Bvirus X-associated protein, XAP3, is a protein
, 百拇医药
kinase C-binding protein. J Biol Chem 1997;272:16482-16489
33 Cross JC, Wen P, Rutter WJ. Transactivation by hepatitis B virus Xprotein is promiscuous and dependent on
mitogen activated cellular serine/threoninekinases. Proc Natl Acad Sci USA 1993;90:8078-8082
34 Doria M, Klein N, Lucito R, Schneider RJ. The hepatitis B virus HBxprotein is a dual specificity cytoplasmic activator of
, http://www.100md.com
Ras and nuclear activator of transcriptionfactors. EMBO J 1995;14:4747-4757
35 Wang HD, Trivedi A, Johnson DL. Hepatitis B virus X protein inducesRNA polymerase III-dependent gene transcription
and increases cellular TATA-binding proteinby activating the Ras signaling pathway. Mol Cell Biol 1997;17:6838-6846
36 Benn J, Schneider RJ. Hepatitis B virus HBx protein deregulatescell cycle checkpoint controls. Proc Natl Acad Sci
, 百拇医药
USA 1995;92:11215-11219
37 Miller DM, Rahill BM, Boss JM, Lairmore MD, Durbin JE, Waldman JW,Sedmak DD. Human cytomegalovirus inhibits
major histocompatibility complex class IIexpression by disruption of the Jak/Stat pathway. J Exp Med
1998;187:675-683
38 Velazquez L, Fellous M, Stark GR, Pellegrini S. A protein tyrosinekinase in the interferon alpha/beta signaling
, http://www.100md.com
pathway. Cell 1992;70:313-322
39 Heim MH, Moradpour D, Blum HE. Expression of hepatitis C virusproteins inhibits signal transduction through the jak-
STAT pathway. J Virol 1999;73:8469-8475
40 Kato N, Yoshida H, Kioko Ono-Nita S, Kato J, Goto T, Otsuka M, LanK, Matsushima K, Shiratori Y, Omata M. Activation
of intracellular signaling by hepatitis Band C viruses: C-viral core is the most potent signal inducer. Hepatology
2000;32:405-412
41 Yoshida T, Hanada T, Tokuhisa T, Kosai K, Sata M, Kohara M,Yoshimura A. Activation of STAT3 by the hepatitis C
virus core protein leads to cellulartransformation. J Exp Med 2002;5:641-653, 百拇医药( 张忠东, 成 军, 钟彦伟, 张树林)
