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Molecular and Cellular Biology, September 1998, p. 5219-5228, Vol. 18, No. 9
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Identification of an Immunoreceptor Tyrosine-Based Activation Motif of K1 Transforming Protein of Kaposi's Sarcoma-Associated Herpesvirus

Heuiran Lee,1 Jie Guo,1 Mengtao Li,1 Joong-Kook Choi,1 Maryann DeMaria,2 Michael Rosenzweig,2 and Jae U. Jung1,*

Department of Microbiology and Molecular Genetics1 and Department of Immunology,2 New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772

Received 14 January 1998/Returned for modification 23 March 1998/Accepted 12 June 1998

Kaposi's sarcoma-associated herpesvirus (KSHV) is consistently identified in Kaposi's sarcoma and body cavity-based lymphoma. KSHV encodes a transforming protein called K1 which is structurally similar to lymphocyte receptors. We have found that a highly conserved region of the cytoplasmic domain of K1 resembles the sequence of immunoreceptor tyrosine-based activation motifs (ITAMs). To demonstrate the signal-transducing activity of K1, we constructed a chimeric protein in which the cytoplasmic tail of the human CD8alpha polypeptide was replaced with that of KSHV K1. Expression of the CD8-K1 chimera in B cells induced cellular tyrosine phosphorylation and intracellular calcium mobilization upon stimulation with an anti-CD8 antibody. Mutational analyses showed that the putative ITAM of K1 was required for its signal-transducing activity. Furthermore, tyrosine residues of the putative ITAM of K1 were phosphorylated upon stimulation, and this allowed subsequent binding 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 activation.

* Corresponding author. Mailing address: New England Regional Primate Research Center, 1 Pine Hill Dr., Southborough, MA 01772. Phone: (508) 624-8083. Fax: (508) 624-8190. E-mail: jjung{at}warren.med.harvard.edu.

Molecular and Cellular Biology, September 1998, p. 5219-5228, Vol. 18, No. 9
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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