T. Lund et al., HERPESVIRUS SAIMIRI TIP-484 MEMBRANE-PROTEIN MARKEDLY INCREASES P56(LCK) ACTIVITY IN T-CELLS, Journal of virology, 71(1), 1997, pp. 378-382
Herpesvirus saimiri (HVS) is a T-cell-specific transforming and oncoge
nic virus, A protein encoded by RVS known as Tip-484 (for tyrosine kin
ase interacting protein from HVS strain 484) is required for this tran
sformation. Tip-484 binds specifically to the nonreceptor protein tyro
sine kinase p56(lck). By transfecting Tip-484 into T cells, we now sho
w that this interaction leads to a several hundred-fold increase in th
e kinase activity of p56(lck). Tip-484 is part of a protein complex wh
ich is dependent on the presence of p56(lck) and is phosphorylated. We
also show that two of the complexed proteins represent two phosphoryl
ated forms of Tip-484. Furthermore, the p56(lck) kinase activity in HV
S-infected human peripheral blood T lymphocytes was at least ninefold
higher than that in noninfected control cells and significantly decrea
sed in cells infected with a Tip-484 deletion mutant virus. Finally, w
e report that Tip-484 is required for oncogenesis in rabbits by the su
rvival of rabbits inoculated with Tip-484 deletion mutant HVS. The dat
a demonstrate dramatic stimulation of the signaling pathway of p56(lck
). This effect can contribute to the molecular mechanisms that lead to
sustained autocrine secretion of growth factors, permanent T-cell gro
wth, and ultimately lymphocytic tumor formation.