Deregulated signal transduction by the K1 gene product of Kaposi's sarcoma-associated herpesvirus.
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 K1 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 K1 involves classical syk and phospholipase C gamma2 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.
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002645:Chickens; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D017930:Genes, Reporter; D019288:Herpesvirus 8, Human / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000378:metabolism; D009842:Oligopeptides; D010455:Peptides / Q000276:immunology; D051966:Phospholipase C gamma; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000821:virology*; D015398:Signal Transduction / Q000235:genetics; D000072377:Syk Kinase; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism*