IDENTIFICATION OF AN IMMUNORECEPTOR TYROSINE-BASED ACTIVATION MOTIF OF K1 TRANSFORMING PROTEIN OF KAPOSIS SARCOMA-ASSOCIATED HERPESVIRUS

Kaposi's sarcoma-associated herpesvirus (KSHV) is consistently identif ied in Kaposi's sarcoma and body cavity-based lymphoma. KSHV encodes a transforming protein called K1 which is structurally similar to lymph ocyte receptors. We have found that a highly conserved region of the c ytoplasmic domain of K1 resembles the sequence of immunoreceptor tyros ine-based activation motifs (ITAMs). To demonstrate the signal-transdu cing activity of K1, we constructed a chimeric protein in which the cy toplasmic tail of the human CD8 alpha. polypeptide was replaced with t hat of KSHV K1. Expression of the CD8-K1 chimera in B cells induced ce llular tyrosine phosphorylation and intracellular calcium mobilization upon stimulation with an anti-CDS antibody. Mutational analyses showe d that the putative ITAM of K1 was required for its signal-transducing activity. Furthermore, tyrosine residues of the putative ITAM of K1 w ere phosphorylated upon stimulation, and this allowed subsequent bindi ng 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 activatio n.