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 CD8` 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 PUBLICATIONS Lee, H, Guo, J, Li, M , Choi, J-K, DeMaria, M, Rosenzweig, M, and Jung, JU Identification of an immunoreceptor tyrosine-based activation motif of K1 transforming protein of Kaposi's sarcoma-associated herpesvirus Mol Cell Biol 1998; 18, 5219-5228

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000168-40
Application #
6453739
Study Section
Project Start
2001-05-01
Project End
2002-04-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
40
Fiscal Year
2001
Total Cost
$111,112
Indirect Cost
Name
Harvard University
Department
Type
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
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