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

AUTOR(ES)

Lagunoff, Michael

FONTE

The National Academy of Sciences

RESUMO

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 γ2 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.

Documentos Relacionados

• Transcriptional Regulation of the K1 Gene Product of Kaposi's Sarcoma-Associated Herpesvirus
• Suppression of Tetradecanoyl Phorbol Acetate-Induced Lytic Reactivation of Kaposi's Sarcoma-Associated Herpesvirus by K1 Signal Transduction
• Structural Analysis of the Kaposi's Sarcoma-Associated Herpesvirus K1 Protein
• The K1 Protein of Kaposi's Sarcoma-Associated Herpesvirus Activates the Akt Signaling Pathway
• Kinetics of Kaposi’s Sarcoma-Associated Herpesvirus Gene Expression