ENHANCED DOWN-REGULATION OF LCK-MEDIATED SIGNAL-TRANSDUCTION BY A Y-114 MUTATION OF HERPESVIRUS SAIMIRI TIP

Tip of herpesvirus saimiri associates with Lck and downregulates Lck f unction in cellular signal transduction, In this report, we demonstrat e that mutation of tyrosine 114 of Tip significantly increases Lck-bin ding activity, This mutant exhibits a dramatic increase in the suppres sion of cellular tyrosine phosphorylation and surface expression of ly mphocyte antigens in comparison with wild-type Tip. In addition, the e xpression of TipY(114) converted the transforming morphology of fibrob lasts induced by oncogenic F505 Lck to a normal cellular morphology, T hese results further support a mechanism by which the association of T ip with Lck negatively regulates Lck-mediated signal transduction.