Deregulated signal transduction by the K1 gene product of Kaposi's sarcoma-associated herpesvirus

被引:117
作者
Lagunoff, M
Majeti, R
Weiss, A
Ganem, D [1 ]
机构
[1] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
关键词
D O I
10.1073/pnas.96.10.5704
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The Kaposi's sarcoma (KS)-associated herpesvirus is a lymphotropic virus strongly implicated in the pathogenesis of KS and several lymphoproliferative disorders. The KS-associated herpesvirus Iii 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 of the full-length K1 protein can initiate calcium-dependent signal transduction in B cells; however, unlike other ITAM-based signal transduction events, K1 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 gl involves classical syk and phospholipase C gamma 2 activation, both ITAM- and syk-independent signaling pathways are activated by K1 expression. These studies indicate that K1 is a deregulated signaling molecule with pleitropic effects that may explain its known growth deregulatory properties.
引用
收藏
页码:5704 / 5709
页数:6
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