MUTATATED LCK BINDING MOTIF FOR LYMPHOID CELL ACTIVATION BY HERPESVIRUS SAIMIRI

疱疹病毒 SAIMIRI 激活淋巴细胞的突变 LCK 结合基序

• 批准号: 6116558
• 负责人: Samuel Monroe DUBOISE
• 金额: $ 11.16万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6116558
• 关键词: animal tissue; communicable diseases; virus

The proline-rich SH3-binding (SH3B) motif of the tyrosine kinase-interacting protein (Tip) of herpesvirus saimiri (HVS) is required for binding to the cellular Src family kinase Lck We constructed a mutant form of HVS in which prolines in the SH3B motif of Tip were altered to alanines This mutant form of Tip was incapable of binding to Lck The mutant virus, HVS/Tip mSH3B, retained its ability to immortalize common marmoset lymphocytes in culture In fact, common marmoset lymphocytes immortalized by the HVS/Tip mSH3B mutant displayed increased expression of HLA-DR lymphocyte activation marker, an altered pattern of tyrosine phosphorylation, increased expression of the tyrosine kinase Lyn, and a shift in electrophoretic mobility of Lck compared to cells immortalized by wild-type HVS Experimental infection of common marmosets resulted in fulminant lymphoma with both HVS/Tip mSH3B and wild-type HVS However, HVS/Tip mSH3B produced greater infiltration of affected or gans by proliferating lymphoid cells compared to wild-type HVS These results demonstrate that Tip binding to Lck is not necessary for transformation and that abrogation of Tip binding to Lck alters the characteristics of transformed cells and the severity of the pathologic lesions PUBLICATIONS Lee, H, Veazey, R, Williams, K, Li, M, Guo, J, Neipel, F, Fleckenstein, B, Lackner, A, Desrosiers, RC, and Jung, JU Mutation of the Lck-binding motif of tip enhances lymphoid cell activation by herpesvirus saimiri J Virol 1998; 72:2607-2614

酪氨酸蛋白富含脯氨酸的SH3结合（SH3B）基序 松鼠猴疱疹病毒（HVS）的激酶相互作用蛋白（Tip）是 需要结合到细胞Src家族激酶Lck我们 构建了突变型HVS，其中SH3B基序中的脯氨酸 这种突变形式的小费是不能 突变病毒HVS/Tip mSH 3B保留了其与Lck结合的能力。 在培养中使普通绒猴淋巴细胞永生化的能力事实上， 通过HVS/Tip mSH3B突变体永生化的普通绒猴淋巴细胞 显示HLA-DR淋巴细胞活化标志物表达增加， 酪氨酸磷酸化模式的改变， 酪氨酸激酶林恩，并在电泳迁移率的变化， Lck与通过野生型HVS永生化的细胞相比 感染普通绒猴导致暴发性淋巴瘤， HVS/Tip mSH3B和野生型HVS然而，HVS/Tip mSH3B产生 受影响的或GAN通过增殖的淋巴细胞的更大的浸润 这些结果表明，提示 与Lck的结合不是转化所必需的， Tip与Lck的结合改变了转化细胞的特性 和病理损伤的严重程度。出版物Lee，H， Veazey，R，威廉姆斯，K，Li，M，Guo，J，Neipel，F，Fleckenstein，B， Lackner，A，Desrosiers，RC和Jung，JU Lck结合的突变 TIP序列增强松鼠猴疱疹病毒对淋巴细胞的激活作用 病毒学杂志1998; 72：2607 - 2614