MUTATATED LCK BINDING MOTIF FOR LYMPHOID CELL ACTIVATION BY HERPESVIRUS SAIMIRI

酪氨酸的富含脯氨酸的SH3结合基序(SH3B) 疱疹病毒塞米里病毒的蛋白结合蛋白(TIP)是 与细胞内Src家族激酶Lck We结合所需 构建了SH3B基序中含有脯氨酸的人类视觉系统的突变形式 的TIP被改变为丙氨酸这种突变形式的TIP不能 与Lck结合的突变病毒HVS/Tip mSH3B保留了其 事实上，在培养中使普通的绒猴淋巴细胞永生的能力， HVS/Tip mSH3B突变体使常见绒猴淋巴细胞永生化 表现为HLA-DR淋巴细胞活化标志物表达增加， 酪氨酸磷酸化模式改变，表达增加 酪氨酸激酶Lyn的活性和凝胶迁移率的变化。 LCK与野生型HVS实验永生化细胞的比较 感染普通绒猴导致暴发性淋巴瘤，两者均有 然而，HVS/Tip mSH3B和野生型HVS产生了 淋巴组织增殖性淋巴组织对受影响的细菌有更大的渗透 细胞与野生型HV的比较这些结果表明TIP 与Lck的结合不是转化和废除所必需的 TIP与Lck结合改变转化细胞的特性 以及病理损害的严重程度发表在Lee，H， 维兹，R，威廉姆斯，K，李，M，郭，J，内佩尔，F，弗莱肯斯坦，B， Lackner，A，Desrosiers，RC，和Jung，Ju的Lck结合突变 TIP基序通过疱疹病毒SAIMIRI促进淋巴细胞活化 J Virol 1998；72：2607-2614

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