THE PRODUCT OF THE HERPESVIRUS-SAIMIRI OPEN READING FRAME-1 (TIP) INTERACTS WITH T-CELL-SPECIFIC KINASE P56(LCK) IN TRANSFORMED-CELLS

Subgroup C strains of Herpesvirus saimiri, a leukemogenic virus of non human primates, transform human T cells to permanent growth in cultur e, These cells retain their antigen specificity, and they are becoming widely used as a model for activated human T cells, Though a variety of human cell types can be infected by H. saimiri, transformation appe ars to be specific for CD4+ and CD8+ T cells, Our investigation of ear ly signaling events in H. saimiri-transformed T cells revealed a novel 40-kDa phosphoprotein complexed with the T cell-specific tyrosine pro tein kinase p56(lck). This protein, termed Tip (tyrosine kinase intera cting protein), is identified as a viral protein encoded by the open r eading frame 1 (ORF1), In the transformed cells Tip is expressed toget her with the gene product of ORF2, the viral onco protein StpC, which acts on epithelial cells, The H. saimiri genome has 75 ORFs, but only ORF1 and ORF2 are transcribed in transformed human cells, Tip is phosp horylated on tyrosine in cell-free systems containing Lck, indicating that the viral protein is a substrate for this T cell-specific kinase, Alteration of T cell signaling pathways by Tip may be the second even t complementing the action of StpC in a new mechanism of T cell transf ormation.