Enhanced downregulation of Lck-mediated signal transduction by a Y114 mutation of herpesvirus Saimiri tip.
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.
Guo
J
J
Department of Microbiology and Molecular Genetics, New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772-9102, USA.
Duboise
M
M
Lee
H
H
Li
M
M
Choi
J K
JK
Rosenzweig
M
M
Jung
J U
JU
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*
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