The Epstein-Barr virus latent membrane protein 1 putative Janus kinase 3 (JAK3) binding domain does not mediate JAK3 association or activation in B-lymphoma or lymphoblastoid cell lines

Epstein-Barr virus (EBV) latent infection membrane protein 1 (LMP1) has an intermediate domain between the two cytoplasmic carboxyl-terminal domains t hat are critical for transforming B-lymphocytes into lymphoblastoid cell li nes (LCLs). The intermediate domain has been implicated in Janus kinase 3 ( JAK3) association and activation. We now find that LCLs transformed by EBV recombinants that express Flag-LMP1 with the putative JAK3 binding and acti vating intermediate domain deleted and LCLs transformed by Flag-LMP1 EBV re combinants have similar levels of phosphotyrosine-activated JAK3, signal tr ansducer and activator of transcription 3 (STAT3), or STAT5 and similar ver y low levels of JAK3 associated with LMP1. Further, transient Flag-LMP1 exp ression in a B-lymphoma cell line transduces signals that upregulate TRAF1 levels but does not alter JAK3 levels or activation state. Although these d ata indicate that the LMP1 putative JAK3 binding and activating intermediat e domain does not mediate JAK3 association or activation in B-lymphocytes, JAK3 association with LMP1 could be significant, particularly in cells in w hich LMP1, JAK3, or a JAK3-associated protein is expressed at high levels.