{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T22:17:23Z","timestamp":1779920243122,"version":"3.53.1"},"reference-count":65,"publisher":"Microbiology Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,5,1]]},"abstract":"<jats:p>Hepatitis C virus (HCV) is the major causative agent of hepatocellular carcinoma. However, the precise mechanism underlying the carcinogenesis is yet to be elucidated. It has recently been reported that Syk, a non-receptor protein tyrosine kinase, functions as a potent tumour suppressor in human breast carcinoma. This study first examined the possible effect of HCV infection on expression of Syk<jats:italic>in vivo<\/jats:italic>. Immunohistochemical analysis revealed that endogenous Syk, which otherwise was expressed diffusely in the cytoplasm of normal hepatocytes, was localized near the cell membrane with a patchy pattern in HCV-infected hepatocytes. The possible interaction between HCV proteins and Syk in human hepatoma-derived Huh-7 cells was then examined. Immunoprecipitation analysis revealed that NS5A interacted strongly with Syk. Deletion-mutation analysis revealed that an N-terminal portion of NS5A (aa\u20051\u2013175) was involved in the physical interaction with Syk. An<jats:italic>in vitro<\/jats:italic>kinase assay demonstrated that NS5A inhibited the enzymic activity of Syk and that, in addition to the N-terminal 175 residues, a central portion of NS5A (aa\u2005237\u2013302) was required for inhibition of Syk. Moreover, Syk-mediated phosphorylation of phospholipase C-<jats:italic>\u03b3<\/jats:italic>1 was downregulated by NS5A. An interaction of NS5A with Syk was also detected in Huh-7.5 cells harbouring an HCV RNA replicon or infected with HCV. In conclusion, these results demonstrated that NS5A interacts with Syk resulting in negative regulation of its kinase activity. The results indicate that NS5A may be involved in the carcinogenesis of hepatocytes through the suppression of Syk kinase activities.<\/jats:p>","DOI":"10.1099\/vir.0.83510-0","type":"journal-article","created":{"date-parts":[[2008,4,17]],"date-time":"2008-04-17T17:33:51Z","timestamp":1208453631000},"page":"1231-1242","source":"Crossref","is-referenced-by-count":20,"title":["Hepatitis C virus NS5A protein interacts with and negatively regulates the non-receptor protein tyrosine kinase Syk"],"prefix":"10.1099","volume":"89","author":[{"given":"Sachiko","family":"Inubushi","sequence":"first","affiliation":[{"name":"Division of Microbiology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoko","family":"Nagano-Fujii","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kikumi","family":"Kitayama","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motofumi","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunying","family":"An","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Yokozaki","sequence":"additional","affiliation":[{"name":"Division of Surgical Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirohei","family":"Yamamura","sequence":"additional","affiliation":[{"name":"Hyogo Laboratory, Hyogo Prefectural Institute of Public Health and Environmental Sciences, Kobe 652-0032, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideko","family":"Nuriya","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Cell Biology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michinori","family":"Kohara","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Cell Biology, The Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyonao","family":"Sada","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hak","family":"Hotta","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"crossref","first-page":"13001","DOI":"10.1128\/JVI.76.24.13001-13014.2002","article-title":"Highly permissive cell lines for subgenomic and genomic hepatitis C virus RNA replication","volume":"76","author":"Blight","year":"2002","journal-title":"J Virol"},{"key":"R2","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/378303a0","article-title":"Syk tyrosine kinase required for mouse viability and B-cell development","volume":"378","author":"Cheng","year":"1995","journal-title":"Nature"},{"key":"R3","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1126\/science.2523562","article-title":"Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome","volume":"244","author":"Choo","year":"1989","journal-title":"Science"},{"key":"R4","doi-asserted-by":"crossref","first-page":"5233","DOI":"10.1128\/JVI.74.11.5233-5241.2000","article-title":"Nonstructural protein 5A of hepatitis C virus inhibits the function of karyopherin \u03b2 3","volume":"74","author":"Chung","year":"2000","journal-title":"J Virol"},{"key":"R5","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1038\/35021086","article-title":"The Syk tyrosine kinase suppresses malignant growth of human breast cancer cells","volume":"406","author":"Coopman","year":"2000","journal-title":"Nature"},{"key":"R6","doi-asserted-by":"crossref","first-page":"4683","DOI":"10.1073\/pnas.91.11.4683","article-title":"Granulocyte colony-stimulating factor receptor signaling involves the formation of a three-component complex with Lyn and Syk protein-tyrosine kinases","volume":"91","author":"Corey","year":"1994","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R7","first-page":"2595","article-title":"Critical role for the tyrosine kinase Syk in signalling through the high affinity IgE receptor of mast cells","volume":"13","author":"Costello","year":"1996","journal-title":"Oncogene"},{"key":"R8","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1099\/vir.0.81735-0","article-title":"NS3 protein of hepatitis C virus associates with the tumor suppressor p53 and inhibits its function in an NS3 sequence-dependent manner","volume":"87","author":"Deng","year":"2006","journal-title":"J Gen Virol"},{"key":"R9","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1128\/JCM.34.3.569-574.1996","article-title":"Hepatitis C virus (HCV) subtype prevalence in Chiang Mai, Thailand, and identification of novel subtypes of HCV major type 6","volume":"34","author":"Doi","year":"1996","journal-title":"J Clin Microbiol"},{"key":"R10","doi-asserted-by":"crossref","first-page":"13038","DOI":"10.1073\/pnas.0405152101","article-title":"Phosphorylation of hepatitis C virus nonstructural protein 5A modulates its protein interactions and viral RNA replication","volume":"101","author":"Evans","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R11","doi-asserted-by":"crossref","first-page":"5208","DOI":"10.1128\/MCB.18.9.5208","article-title":"Control of PKR protein kinase by hepatitis C virus nonstructural 5A protein: molecular mechanisms of kinase regulation","volume":"18","author":"Gale","year":"1998","journal-title":"Mol Cell Biol"},{"key":"R12","doi-asserted-by":"crossref","first-page":"6414","DOI":"10.1093\/emboj\/16.21.6414","article-title":"Regulation of the pp72syk protein tyrosine kinase by platelet integrin \u03b1 IIb \u03b2 3","volume":"16","author":"Gao","year":"1997","journal-title":"EMBO J"},{"key":"R13","doi-asserted-by":"crossref","first-page":"3480","DOI":"10.1128\/JVI.78.7.3480-3488.2004","article-title":"Interactions between viral nonstructural proteins and host protein hVAP-33 mediate the formation of hepatitis C virus RNA replication complex on lipid raft","volume":"78","author":"Gao","year":"2004","journal-title":"J Virol"},{"key":"R14","doi-asserted-by":"crossref","first-page":"7184","DOI":"10.1074\/jbc.275.10.7184","article-title":"Hepatitis C virus NS5A protein modulates transcription through a novel cellular transcription factor SRCAP","volume":"275","author":"Ghosh","year":"2000","journal-title":"J Biol Chem"},{"key":"R15","doi-asserted-by":"crossref","first-page":"3969","DOI":"10.1038\/sj.onc.1204515","article-title":"Spleen tyrosine kinase (Syk) deficiency in childhood pro-B cell acute lymphoblastic leukemia","volume":"20","author":"Goodman","year":"2001","journal-title":"Oncogene"},{"key":"R16","doi-asserted-by":"crossref","first-page":"13473","DOI":"10.1128\/JVI.79.21.13473-13482.2005","article-title":"Human VAP-B is involved in hepatitis C virus replication through interaction with NS5A and NS5B","volume":"79","author":"Hamamoto","year":"2005","journal-title":"J Virol"},{"key":"R17","doi-asserted-by":"crossref","first-page":"9207","DOI":"10.1128\/JVI.76.18.9207-9217.2002","article-title":"Subversion of cell signaling pathways by hepatitis C virus nonstructural 5A protein via interaction with Grb2 and P85 phosphatidylinositol 3-kinase","volume":"76","author":"He","year":"2002","journal-title":"J Virol"},{"key":"R18","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1099\/vir.0.80862-0","article-title":"Hepatitis C virus NS3 protein interacts with ELKS- \u03b4 and ELKS- \u03b1 , members of a novel protein family involved in intracellular transport and secretory pathways","volume":"86","author":"Hidajat","year":"2005","journal-title":"J Gen Virol"},{"key":"R19","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1006\/bbrc.1994.2667","article-title":"Production of two phosphoproteins from the NS5A region of the hepatitis C viral genome","volume":"205","author":"Kaneko","year":"1994","journal-title":"Biochem Biophys Res Commun"},{"key":"R20","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1084\/jem.182.6.1815","article-title":"Role of the Syk autophosphorylation site and SH2 domains in B cell antigen receptor signaling","volume":"182","author":"Kurosaki","year":"1995","journal-title":"J Exp Med"},{"key":"R21","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1128\/MCB.16.4.1305","article-title":"Phospholipase C- \u03b3 1 interacts with conserved phosphotyrosyl residues in the linker region of Syk and is a substrate for Syk","volume":"16","author":"Law","year":"1996","journal-title":"Mol Cell Biol"},{"key":"R22","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1002\/ijc.21074","article-title":"Growth-related oncogene produced in human breast cancer cells and regulated by Syk protein-tyrosine kinase","volume":"117","author":"Li","year":"2005","journal-title":"Int J Cancer"},{"key":"R23","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1126\/science.1114016","article-title":"Complete replication of hepatitis C virus in cell culture","volume":"309","author":"Lindenbach","year":"2005","journal-title":"Science"},{"key":"R24","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1128\/JVI.75.3.1437-1449.2001","article-title":"Mutations in hepatitis C virus RNAs conferring cell culture adaptation","volume":"75","author":"Lohmann","year":"2001","journal-title":"J Virol"},{"key":"R25","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1099\/vir.0.80204-0","article-title":"Hepatitis C virus NS5A: tales of a promiscuous protein","volume":"85","author":"Macdonald","year":"2004","journal-title":"J Gen Virol"},{"key":"R26","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1099\/vir.0.19691-0","article-title":"The hepatitis C virus NS5A protein binds to members of the Src family of tyrosine kinases and regulates kinase activity","volume":"85","author":"Macdonald","year":"2004","journal-title":"J Gen Virol"},{"key":"R27","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1111\/j.1478-3231.2004.0909.x","article-title":"Hepatitis C virus infection in human liver tissue engrafted in mice with an infectious molecular clone","volume":"24","author":"Maeda","year":"2004","journal-title":"Liver Int"},{"key":"R28","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1128\/JVI.75.3.1401-1407.2001","article-title":"Hepatitis C virus NS5A physically associates with p53 and regulates p21\/waf1 gene expression in a p53-dependent manner","volume":"75","author":"Majumder","year":"2001","journal-title":"J Virol"},{"key":"R29","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1099\/0022-1317-76-10-2493","article-title":"Investigation of the pattern of hepatitis C virus sequence diversity in different geographical regions: implications for virus classification","volume":"76","author":"Mellor","year":"1995","journal-title":"J Gen Virol"},{"key":"R30","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1128\/MCB.24.1.71-83.2004","article-title":"Activation of Syk protein tyrosine kinase in response to osmotic stress requires the interaction with p21-activated protein kinase Pak2\/ \u03b3 -PAK","volume":"24","author":"Miah","year":"2004","journal-title":"Mol Cell Biol"},{"key":"R31","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1038\/ncb1631","article-title":"The lipid droplet is an important organelle for hepatitis C virus production","volume":"9","author":"Miyanari","year":"2007","journal-title":"Nat Cell Biol"},{"key":"R32","doi-asserted-by":"crossref","first-page":"4954","DOI":"10.1128\/JVI.71.7.4954-4961.1997","article-title":"Nuclear localization of the NS3 protein of hepatitis C virus and factors affecting the localization","volume":"71","author":"Muramatsu","year":"1997","journal-title":"J Virol"},{"key":"R33","doi-asserted-by":"crossref","first-page":"6370","DOI":"10.1128\/JVI.78.12.6370-6380.2004","article-title":"Intramembrane proteolysis and endoplasmic reticulum retention of hepatitis C virus core protein","volume":"78","author":"Okamoto","year":"2004","journal-title":"J Virol"},{"key":"R34","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1093\/emboj\/16.9.2333","article-title":"The Fc receptor \u03b3 -chain and the tyrosine kinase Syk are essential for activation of mouse platelets by collagen","volume":"16","author":"Poole","year":"1997","journal-title":"EMBO J"},{"key":"R35","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0167-4889(02)00315-4","article-title":"Hepatitis C virus NS5A protein binds TBP and p53, inhibiting their DNA binding and p53 interactions with TBP and ERCC3","volume":"1592","author":"Qadri","year":"2002","journal-title":"Biochim Biophys Acta"},{"key":"R36","first-page":"55","article-title":"Overview of hepatitis C virus genome structure, polyprotein processing, and protein properties","volume":"242","author":"Reed","year":"2000","journal-title":"Curr Top Microbiol Immunol"},{"key":"R37","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1007\/s007050050479","article-title":"Classification, nomenclature, and database development for hepatitis C virus (HCV) and related virus: proposals for standardization","volume":"143","author":"Robertson","year":"1998","journal-title":"Arch Virol"},{"key":"R38","doi-asserted-by":"crossref","first-page":"338","DOI":"10.4049\/jimmunol.164.1.338","article-title":"Point mutation of a tyrosine in the linker region of Syk results in a gain of function","volume":"164","author":"Sada","year":"2000","journal-title":"J Immunol"},{"key":"R39","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1093\/oxfordjournals.jbchem.a002970","article-title":"Structure and function of Syk protein-tyrosine kinase","volume":"130","author":"Sada","year":"2001","journal-title":"J Biochem"},{"key":"R40","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.jim.2004.06.014","article-title":"A novel assay to quantify cell death after transient expression of apoptotic genes in B- and T-lymphocytes","volume":"292","author":"Schneider","year":"2004","journal-title":"J Immunol Methods"},{"key":"R41","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1006\/viro.2001.1225","article-title":"Hepatitis C virus NS5A colocalizes with the core protein on lipid droplets and interacts with apolipoproteins","volume":"292","author":"Shi","year":"2002","journal-title":"Virology"},{"key":"R42","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1128\/MCB.15.1.272","article-title":"Interaction of p72 syk with the \u03b3 and \u03b2 subunits of the high-affinity receptor for immunoglobulin E, Fc\u03f5RI","volume":"15","author":"Shiue","year":"1995","journal-title":"Mol Cell Biol"},{"key":"R43","doi-asserted-by":"crossref","first-page":"4510","DOI":"10.1074\/jbc.M410326200","article-title":"Distinct roles for the linker region tyrosines of Syk in Fc\u03f5RI signaling in primary mast cells","volume":"280","author":"Simon","year":"2005","journal-title":"J Biol Chem"},{"key":"R44","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1099\/0022-1317-80-4-879","article-title":"The NS5A protein of hepatitis C virus partially inhibits the antiviral activity of interferon","volume":"80","author":"Song","year":"1999","journal-title":"J Gen Virol"},{"key":"R45","doi-asserted-by":"crossref","first-page":"12232","DOI":"10.1074\/jbc.M312245200","article-title":"The hepatitis C virus NS5A protein activates a phosphoinositide 3-kinase-dependent survival signaling cascade","volume":"279","author":"Street","year":"2004","journal-title":"J Biol Chem"},{"key":"R46","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1099\/vir.0.19513-0","article-title":"Hepatitis C virus NS5A protein interacts with 2\u2032,5\u2032-oligoadenylate synthetase and inhibits antiviral activity of IFN in an IFN sensitivity-determining region-independent manner","volume":"85","author":"Taguchi","year":"2004","journal-title":"J Gen Virol"},{"key":"R47","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1111\/j.1348-0421.2004.tb03556.x","article-title":"Suppression of hepatitis C virus replicon by RNA interference directed against the NS3 and NS5B regions of the viral genome","volume":"48","author":"Takigawa","year":"2004","journal-title":"Microbiol Immunol"},{"key":"R48","doi-asserted-by":"crossref","first-page":"5533","DOI":"10.1073\/pnas.96.10.5533","article-title":"NS5A, a nonstructural protein of hepatitis C virus, binds growth factor receptor-bound protein 2 adaptor protein in a Src homology 3 domain\/ligand-dependent manner and perturbs mitogenic signaling","volume":"96","author":"Tan","year":"1999","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R49","doi-asserted-by":"crossref","first-page":"15790","DOI":"10.1016\/S0021-9258(18)98478-4","article-title":"Molecular cloning of a porcine gene syk that encodes a 72-kDa protein-tyrosine kinase showing high susceptibility to proteolysis","volume":"266","author":"Taniguchi","year":"1991","journal-title":"J Biol Chem"},{"key":"R50","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/nature03580","article-title":"Structure of the zinc-binding domain of an essential component of the hepatitis C virus replicase","volume":"435","author":"Tellinghuisen","year":"2005","journal-title":"Nature"},{"key":"R51","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1093\/oxfordjournals.jbchem.a022610","article-title":"Purification of a 72-kDa protein-tyrosine kinase from rat liver and its identification as Syk: involvement of Syk in signaling events of hepatocytes","volume":"127","author":"Tsuchida","year":"2000","journal-title":"J Biochem"},{"key":"R52","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/378298a0","article-title":"Perinatal lethality and blocked B-cell development in mice lacking the tyrosine kinase Syk","volume":"378","author":"Turner","year":"1995","journal-title":"Nature"},{"key":"R53","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/S0167-5699(99)01574-1","article-title":"Tyrosine kinase SYK: essential functions for immunoreceptor signalling","volume":"21","author":"Turner","year":"2000","journal-title":"Immunol Today"},{"key":"R54","doi-asserted-by":"crossref","first-page":"L497","DOI":"10.1152\/ajplung.00246.2004","article-title":"Syk tyrosine kinase participates in \u03b2 1-integrin signaling and inflammatory responses in airway epithelial cells","volume":"288","author":"Ulanova","year":"2005","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"R55","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.3748\/wjg.v10.i12.1815","article-title":"Hypermethylation of Syk gene in promoter region associated with oncogenesis and metastasis of gastric carcinoma","volume":"10","author":"Wang","year":"2004","journal-title":"World J Gastroenterol"},{"key":"R56","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/0092-8674(94)90334-4","article-title":"Signal transduction by lymphocyte antigen receptors","volume":"76","author":"Weiss","year":"1994","journal-title":"Cell"},{"key":"R57","doi-asserted-by":"crossref","first-page":"7865","DOI":"10.1073\/pnas.93.15.7865","article-title":"Evidence for a preformed transducer complex organized by the B cell antigen receptor","volume":"93","author":"Wienands","year":"1996","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R58","doi-asserted-by":"crossref","first-page":"538","DOI":"10.4049\/jimmunol.166.1.538","article-title":"Protein-tyrosine kinase Syk expressed in human nasal fibroblasts and its effect on RANTES production","volume":"166","author":"Yamada","year":"2001","journal-title":"J Immunol"},{"key":"R59","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/0898-6568(94)00088-S","article-title":"The structure and function of nonreceptor tyrosine kinase p72SYK expressed in hematopoietic cells","volume":"7","author":"Yanagi","year":"1995","journal-title":"Cell Signal"},{"key":"R60","doi-asserted-by":"crossref","first-page":"2869","DOI":"10.1182\/blood.V98.9.2869","article-title":"Syk expression in endothelial cells and their morphologic defects in embryonic Syk-deficient mice","volume":"98","author":"Yanagi","year":"2001","journal-title":"Blood"},{"key":"R61","doi-asserted-by":"crossref","first-page":"6048","DOI":"10.1128\/JVI.72.7.6048-6055.1998","article-title":"The native form and maturation process of hepatitis C virus core protein","volume":"72","author":"Yasui","year":"1998","journal-title":"J Virol"},{"key":"R62","first-page":"5558","article-title":"Hypermethylation leads to silencing of the SYK gene in human breast cancer","volume":"61","author":"Yuan","year":"2001","journal-title":"Cancer Res"},{"key":"R63","doi-asserted-by":"crossref","first-page":"6687","DOI":"10.1158\/1078-0432.CCR-06-0921","article-title":"Frequent epigenetic inactivation of spleen tyrosine kinase gene in human hepatocellular carcinoma","volume":"12","author":"Yuan","year":"2006","journal-title":"Clin Cancer Res"},{"key":"R64","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1099\/vir.0.18801-0","article-title":"Identification and characterization of amphiphysin II as a novel cellular interaction partner of the hepatitis C virus NS5A protein","volume":"84","author":"Zech","year":"2003","journal-title":"J Gen Virol"},{"key":"R65","doi-asserted-by":"crossref","first-page":"8144","DOI":"10.1128\/MCB.22.23.8144-8154.2002","article-title":"Phosphorylation of Tyr342 in the linker region of Syk is critical for Fc-\u03f5RI signaling in mast cells","volume":"22","author":"Zhang","year":"2002","journal-title":"Mol Cell Biol"}],"container-title":["Journal of General Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jgv\/10.1099\/vir.0.83510-0?crawler=true","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T10:15:20Z","timestamp":1631096120000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/jgv\/10.1099\/vir.0.83510-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,5,1]]},"references-count":65,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2008,5,1]]}},"URL":"https:\/\/doi.org\/10.1099\/vir.0.83510-0","relation":{},"ISSN":["0022-1317","1465-2099"],"issn-type":[{"value":"0022-1317","type":"print"},{"value":"1465-2099","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,5,1]]}}}