HERPESVIRUS SAIMIRI STP W/ TRAFS IN NF KB ACTIVATION & LYMPHOCYTE TRANSFORMATION

卡波西肉瘤相关疱疹病毒(KSHV)一直是 Kaposi肉瘤和体腔淋巴瘤KSHV的鉴定 编码一种结构相似的名为K1的转化蛋白 对于淋巴细胞受体，我们发现了一个高度保守的区域 K1的细胞质结构域的序列类似于 免疫受体酪氨酸激活基序(ITAM)展示 K1的信号转导活性，我们构建了一个嵌合体 人CD8‘多肽胞质尾部所在的蛋白质 被CD8-K1嵌合体的KSHV K1表达所取代 B细胞诱导细胞内酪氨酸磷酸化和细胞内 抗CD8抗体刺激下的钙动员 突变分析表明，K1的ITAM可能是必需的 由于其信号转导活性，此外，酪氨酸残基 K1的假定的ITAM在刺激下被磷酸化，这 允许包含SH2的蛋白的后续结合 证明KSHV转化蛋白K1含有一个 ITAM在其细胞质结构域中的功能以及它可以转导 诱导细胞激活的信号，发表于Lee，H，Guo，J，Li M，Choi，J-K，DeMaria，M，Rosenzweig，M，Jung，Ju鉴定 基于免疫受体酪氨酸的K1激活基序的研究 卡波西肉瘤相关疱疹病毒小鼠的转化蛋白 细胞生物学1998；18,5219-5228

Kaposi's sarcoma-associated herpesvirus (KSHV) is consistently identified in Kaposi's sarcoma and body cavity-based lymphoma KSHV encodes a transforming protein called K1 which is structurally similar to lymphocyte receptors We have found that a highly conserved region of the cytoplasmic domain of K1 resembles the sequence of immunoreceptor tyrosine-based activation motifs (ITAMs) To demonstrate the signal-transducing activity of K1, we constructed a chimeric protein in which the cytoplasmic tail of the human CD8` polypeptide was replaced with that of KSHV K1 Expression of the CD8-K1 chimera in B cells induced cellular tyrosine phosphorylation and intracellular calcium mobilization upon stimulation with an anti-CD8 antibody Mutational analyses showed that the putative ITAM of K1 was required for its signal-transducing activity Furthermore, tyrosine residues of the putative ITAM of K1 were phosphorylated upon stimulation, and this allowed subsequent binding of SH2 -containing proteins These results demonstrate that the KSHV transforming protein K1 contains a functional ITAM in its cytoplasmic domain and that it can transduce signals to induce cellular activation PUBLICATIONS Lee, H, Guo, J, Li, M , Choi, J-K, DeMaria, M, Rosenzweig, M, and Jung, JU Identification of an immunoreceptor tyrosine-based activation motif of K1 transforming protein of Kaposi's sarcoma-associated herpesvirus Mol Cell Biol 1998; 18, 5219-5228