title: Enhanced downregulation of Lck-mediated signal transduction by a Y114 mutation of herpesvirus Saimiri tip.
abstract: Tip of herpesvirus saimiri associates with Lck and downregulates Lck function in cellular signal transduction. In this report, we demonstrate that mutation of tyrosine 114 of Tip significantly increases Lck-binding activity. This mutant exhibits a dramatic increase in the suppression of cellular tyrosine phosphorylation and surface expression of lymphocyte antigens in comparison with wild-type Tip. In addition, the expression of TipY114 converted the transforming morphology of fibroblasts induced by oncogenic F505 Lck to a normal cellular morphology. These results further support a mechanism by which the association of Tip with Lck negatively regulates Lck-mediated signal transduction.
authors.affiliation: Department of Microbiology and Molecular Genetics, New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772-9102, USA.
authors.forename: J
authors.initials: J
authors.lastname: Guo
authors.forename: M
authors.initials: M
authors.lastname: Duboise
authors.forename: H
authors.initials: H
authors.lastname: Lee
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.forename: J K
authors.initials: JK
authors.lastname: Choi
authors.forename: M
authors.initials: M
authors.lastname: Rosenzweig
authors.forename: J U
authors.initials: JU
authors.lastname: Jung
mesh_terms: D016475:3T3 Cells; D000818:Animals; D019556:COS Cells; D006567:Herpesvirus 2, Saimiriine / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D010750:Phosphoproteins; D014764:Viral Proteins; C092384:tyrosine kinase interacting protein, Saimiriine herpesvirus 2; D014443:Tyrosine; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases