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

Noah Isakov, Brigitte Biesinger

Research output: Contribution to journalReview articlepeer-review

50 Scopus citations

Abstract

Protein tyrosine kinases (PTKs) are critically involved in signaling pathways that regulate cell growth, differentiation, activation, and transformation: it is not surprising, therefore, that viruses acquired effector molecules targeting these kinases to ensure their own replication and/or persistence. 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 variety of cell surface receptors and is critical for signal transduction from the T-cell antigen receptor (TCR). Consequently, Lck is targeted by regulatory proteins of T-lymphotropic viruses, especially by the Herpesvirus saimiri (HVS) tyrosine kinase interacting protein (Tip). This oncoprotein physically interacts with Lck in HVS transformed t cells and has an impact on its catalytic activity. However; while Tip inhibits Lck activity in stably expressing cell lines, opposite effects were observed in several in vitro systems. At least in part, this complex situation maybe related to the bipartite nature of the interaction surface of the two proteins. Studies on the interrelationships between Lck and its viral partners contribute to the understanding of the mechanisms of T-cell growth regulation, in general, and of viral 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 situations.

Original languageEnglish
Pages (from-to)3413-3421
Number of pages9
JournalEuropean Journal of Biochemistry
Volume267
Issue number12
DOIs
StatePublished - 12 Jul 2000

Keywords

  • Herpesvirus saimiri
  • Lck
  • Signal transduction
  • T-cell transformation
  • Tip

ASJC Scopus subject areas

  • Biochemistry

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this