Open AccessIdentification of an Immunoreceptor Tyrosine-Based Activation Motif of K1 Transforming Protein of Kaposi’s Sarcoma-Associated Herpesvirus
Author(s) -
Heuiran Lee,
Jie Guo,
Mengtao Li,
Joong-Kook Choi,
MaryAnn DeMaria,
Michael Rosenzweig,
Jae U. Jung
Publication year - 1998
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.18.9.5219
Subject(s) - immunoreceptor tyrosine based activation motif , biology , sh2 domain , kaposi's sarcoma associated herpesvirus , tyrosine , phosphorylation , tyrosine phosphorylation , fusion protein , cytoplasm , microbiology and biotechnology , virology , virus , biochemistry , herpesviridae , recombinant dna , gene , viral disease
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 CD8α 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.