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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Deregulated signal transduction by the KI gene product of Kaposi's sarcoma-associated herpesvirus
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Deregulated signal transduction by the KI gene product of Kaposi's sarcoma-associated herpesvirus

机译：卡波济氏肉瘤相关疱疹病毒的KI基因产物引起的信号转导失调

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摘要

The Kaposi's sarcoma (KS) -associated herpesvirus is a lymphotropic virus strongly implicated in the pathogenesis of KS and several lymphoprolifcrative disorders. The KS-associated herpesvirus KI gene encodes a transmembrane protein bearing a functional immunoreceptor tyrosine-based activation motif (ITAM)-like sequence; it previously has been proposed to be important in viral tumorigenesis because its expression can trigger cell proliferation in vitro and in vivo. Here we show that expression or the full-length Kl protein can initiate calcium-dependent signal transduction in B cells; however, un- like other ITAM-based signal transduction events, KI signaling occurs constitutively, in the absence of exogenous crosslinking ligands. This property is caused by its cysteine-rich ectodomain, which when transferred to other consensus ITAMS induces constitutive signaling. Although ITAM- based signaling by KI involves classical syk and phospholipase C r2 activation, both ITAM- and sy-kindependent signaling pathways are activated by KI expression. These studies indicate that KI is a deregulated signaling molccule with pleitropic effects that may explain its known growth deregulatory properties.
机译：卡波西氏肉瘤（KS）相关的疱疹病毒是与KS的发病机理和几种淋巴结核相关的疾病，与之密切相关的淋巴病毒。与KS相关的疱疹病毒KI基因编码一个跨膜蛋白，该蛋白带有一个基于功能性免疫受体酪氨酸的激活基序（ITAM）样序列。以前已经提出它在病毒肿瘤发生中很重要，因为它的表达可以在体外和体内触发细胞增殖。在这里，我们表明表达或全长K1蛋白可以在B细胞中启动钙依赖性信号转导。然而，与其他基于ITAM的信号转导事件不同，KI信号在没有外源性交联配体的情况下组成性地发生。此属性是由其富含半胱氨酸的胞外域引起的，将其转移到其他共识ITAMS时会诱导组成型信号传导。尽管通过KI进行的基于ITAM的信号传导涉及经典的syk和磷脂酶C r2激活，但是依赖于KI表达的ITAM和sy-kin依赖性信号通路均被激活。这些研究表明，KI是具有多效效应的失控信号分子，这可能解释了其已知的生长失调特性。

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