Lck protein tyrosine kinase is a key regulator of T-cell activation and a target for signal intervention by Herpesvirus saimiri and other viral gene products

Protein tyrosine kinases (PTKs) are critically involved in signaling pathwa ys that regulate cell growth, differentiation, activation, and transformati on. It is not surprising, therefore, that viruses acquire effector molecule s targeting these kinases to ensure their own replication and/or persistenc e. This review summarizes our current knowledge on Lck, a member of the Src family of PTK, and its viral interaction partners. Lck plays a key role in T lymphocyte activation and differentiation. It is associated with a varie ty of cell surface receptors and is critical for signal transduction from t he T-cell antigen receptor (TCR). Consequently, Lck is targeted by regulato ry proteins of T-lymphotropic viruses, especially by the Herpesvirus saimir i (HVS) tyrosine kinase interacting protein (Tip). This oncoprotein physica lly interacts with Lck in HVS transformed T cells and has an impact on its catalytic activity. However, while Tip inhibits Lck activity in stably expr essing cell lines, opposite effects were observed in several in vitro syste ms. At least in part, this complex situation may be related to the bipartit e nature of the interaction surface of the two proteins. Studies on the int errelationships between Lck and its viral partners contribute to the unders tanding of the mechanisms of T-cell growth regulation, in general, and of v iral pathogenicity in particular. In addition, understanding the regulation of Lck activity by viral proteins may serve as a basis for the development of new drugs capable of modifying Lck activity in different pathological s ituations.