Herpesvirus saimiri (HVS) is a lymphotropic oncogenic primate virus. In vitro, HVS has the ability to transform human T cells to an interleukin-2 independent phenotype and immortalize them. A protein encoded by HVS known as Tip-484 (for Tyrosine kinase Interacting Protein from HVS strain-484) is required for this transformation. Tip-484 binds specifically to the non-receptor protein tyrosine kinase p56lck. P56lck is a required element in the transduction of activation signals from the T cell receptor to the nucleus. By transfecting Tip-484 into T cells, we now show that the Tip-484/p56lck interaction leads to a dramatic increase in the kinase activity of p56lck. Tip-484 is part of a protein complex which is dependent upon the presence of p56lck and is phosphorylated. We also show that two of the completed proteins represent two phosphorylated forms of Tip-484. Furthermore, the p56lck kinase activity in HVS infected human peripheral blood lymphocytes was at least nine-fold higher than in non-infected control cells, and significantly decreased in cells infected with a Tip-484 deletion mutant virus. The data demonstrate dramatic stimulation of the signaling pathway of p56lck. This effect can contribute to the molecular mechanisms that lead to sustained autocrine secretion of growth factors, permanent T cell growth, and ultimately, lymphocytic tumor formation.
|Original language||English (US)|
|State||Published - Dec 1 1997|