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首页> 外文期刊>Molecular and Cellular Biology >Identification of an Immunoreceptor Tyrosine-Based Activation Motif of K1 Transforming Protein of Kaposi’s Sarcoma-Associated Herpesvirus
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Identification of an Immunoreceptor Tyrosine-Based Activation Motif of K1 Transforming Protein of Kaposi’s Sarcoma-Associated Herpesvirus

机译：识别基于免疫受体酪氨酸的卡波西氏肉瘤相关疱疹病毒K1转化蛋白的活化基序

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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 CD8α 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.
机译：卡波西氏肉瘤相关疱疹病毒（KSHV）在卡波西氏肉瘤和基于体腔的淋巴瘤中得到一致鉴定。 KSHV编码一种称为K1的转化蛋白，其结构类似于淋巴细胞受体。我们已经发现，K1的胞质结构域的高度保守的区域类似于基于免疫受体酪氨酸的激活基序（ITAMs）的序列。为了证明K1的信号转导活性，我们构建了一种嵌合蛋白，其中人CD8α多肽的细胞质尾部被KSHV K1取代。在抗CD8抗体刺激下，B细胞中CD8-K1嵌合体的表达诱导细胞酪氨酸磷酸化和细胞内钙动员。突变分析表明，假定的K1的ITAM是其信号传导活性所必需的。此外，K1的假定ITAM的酪氨酸残基在刺激后会被磷酸化，这使含SH2的蛋白质随后结合在一起。这些结果表明，KSHV转化蛋白K1在其胞质结构域中包含功能性ITAM，并且它可以转导信号以诱导细胞活化。

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