hcv ns5a protein containing potential ligands for both src homology 2 and 3 domains enhances autophosphorylation of src family kinase fyn in b cells丙肝病毒包含潜在的配体对src ns5a蛋白同源性2和3领域提高自身磷酸化的src家族在b细胞激酶菲英岛.pdfVIP
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hcv ns5a protein containing potential ligands for both src homology 2 and 3 domains enhances autophosphorylation of src family kinase fyn in b cells丙肝病毒包含潜在的配体对src ns5a蛋白同源性2和3领域提高自身磷酸化的src家族在b细胞激酶菲英岛
HCV NS5A Protein Containing Potential Ligands for Both
Src Homology 2 and 3 Domains Enhances
Autophosphorylation of Src Family Kinase Fyn in B Cells
1 1,2 1,2 1 1
Kenji Nakashima , Kenji Takeuchi , Kazuyasu Chihara , Tomoko Horiguchi , Xuedong Sun ,
3 3 3 1,2
Lin Deng , Ikuo Shoji , Hak Hotta , Kiyonao Sada *
1 Division of Genome Science and Microbiology, Department of Pathological Sciences, School of Medicine, Faculty of Medical Sciences, University of Fukui, Eiheiji, Japan,
2 Organization for Life Science Advancement Programs, University of Fukui, Eiheiji, Japan, 3 Division of Microbiology, Center for Infectious Diseases, Kobe University
Graduate School of Medicine, Kobe, Japan
Abstract
Hepatitis C virus (HCV) infects B lymphocytes and induces mixed cryoglobulinemia and B cell non-Hodgkin’s lymphoma. The
molecular mechanism for the pathogenesis of HCV infection-mediated B cell disorders remains obscure. To identify the
possible role for HCV nonstructural 5A (NS5A) protein in B cells, we generated the stable B cell lines expressing Myc-His
tagged NS5A. Immunoprecipitation study in the presence or absence of pervanadate (PV) implied that NS5A was tyrosine
phosphorylated by pervanadate (PV) treatment of the cells. Therefore we examined pull-down assay by using glutathione S-
transferase (GST)-fusion proteins of various Src homology 2 (SH2) domains, which associates with phosphotyrosine within a
specific amino acid sequence. The results showed that NS5A specifically bound to SH2 domain of Fyn from PV-treated B
cells in addition to Src homology 3 (SH3) domain. Substitution of Arg176 to Lys in the
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