title: 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.
abstract: Epstein-Barr virus (EBV) latent infection membrane protein 1 (LMP1) has an intermediate domain between the two cytoplasmic carboxyl-terminal domains that are critical for transforming B-lymphocytes into lymphoblastoid cell lines (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 activating intermediate domain deleted and LCLs transformed by Flag-LMP1 EBV recombinants have similar levels of phosphotyrosine-activated JAK3, signal transducer and activator of transcription 3 (STAT3), or STAT5 and similar very low levels of JAK3 associated with LMP1. Further, transient Flag-LMP1 expression in a B-lymphoma cell line transduces signals that upregulate TRAF1 levels but does not alter JAK3 levels or activation state. Although these data indicate that the LMP1 putative JAK3 binding and activating intermediate domain does not mediate JAK3 association or activation in B-lymphocytes, JAK3 association with LMP1 could be significant, particularly in cells in which LMP1, JAK3, or a JAK3-associated protein is expressed at high levels.
authors.affiliation: Channing Laboratory and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115-5804, USA.
authors.forename: Masaya
authors.initials: M
authors.lastname: Higuchi
authors.forename: Elliott
authors.initials: E
authors.lastname: Kieff
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Izumi
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D017353:Gene Deletion; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D053616:Janus Kinase 3; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011995:Recombination, Genetic; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3