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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2008.1
- 수록면
- 566 - 574 (9page)
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Viral proteins of γ-2 herpesviruses, such as LMP2A of Epstein Barr virus (EBV) and Tip of herpesvirus saimiri (HVS) dysregulate lymphocyte signaling by interacting with Src family kinases. K15 open reading frame of Kaposi’s sarcoma associated herpesvirus (KSHV), located at the right end of the viral genome, encodes several splicing variants differing in numbers of transmembrane domains. Previously, we demonstrated that the cytoplasmic tail of the K15 protein interfered with B cell receptor signal transduction to cellular tyrosine phosphorylation and calcium mobilization.
However, the detailed mechanism underlying this phenomenon was not understood. In the C-terminal cytoplasmic region of K15, putative binding domains for Src-SH2 and -SH3 were identified. In this study, we attempted to characterize these modular elements and cellular binding protein(s) by GST pull down and co-immunoprecipitation assays. These studies revealed that K15 interacted with the major B cell tyrosine kinase Lyn. In vitro kinase and transient co-expression assays showed that the expression of K15 protein resulted in activation of Lyn kinase activity. In addition, GST pull down assay suggested that the SH2 domain of Lyn alone was necessary for interaction with the C-terminal SH2B (YEEV) of K15, but the addition of Lyn SH3 to the SH2 domain increases the binding affinity to K15 protein. The data from luciferase assays indicate that K15 expression in BJAB cells induced NFAT and AP1 activities. The tyrosine residue in the C-terminal end of K15 required for the Lyn interaction appeared to be essential for NFAT/AP1 activation, highlighting the significance of the C-terminal SH2B of K15 as a modular element in interfering with B lymphocyte signaling through interaction with Lyn kinase.
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참고문헌 (23)
참고문헌 신청
Brinkmann MM / 2007 / Modulation of host gene expression by the K15 protein of Kaposi's sarcoma-associated herpesvirus / J Virol 81 : 42 ~ 58
Burkhardt AL / 1992 / An Epstein- Barr virus transformation-associated membrane protein interacts with src family tyrosine kinases / J Virol 66 : 5161 ~ 7
Busson P / 1995 / Sequence polymorphism in the Epstein-Barr virus latent membrane protein (LMP)-2 gene / J Gen Virol 76 : 139 ~ 45
Cesarman E / 1995 / Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas / N Engl J Med 332 : 1186 ~ 91
Chan VW / 1997 / Characterization of the B lymphocyte populations in Lyn-deficient mice and the role of Lyn in signal initiation and down-regulation / Immunity 7 : 69 ~ 81
Burkhardt AL / 1992 / An Epstein- Barr virus transformation-associated membrane protein interacts with src family tyrosine kinases / J Virol 66 : 5161 ~ 7
Busson P / 1995 / Sequence polymorphism in the Epstein-Barr virus latent membrane protein (LMP)-2 gene / J Gen Virol 76 : 139 ~ 45
Cesarman E / 1995 / Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas / N Engl J Med 332 : 1186 ~ 91
Chan VW / 1997 / Characterization of the B lymphocyte populations in Lyn-deficient mice and the role of Lyn in signal initiation and down-regulation / Immunity 7 : 69 ~ 81
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