The Lck Binding Domain of Herpesvirus Saimiri Tip-484 Constitutively Activates Lck and STAT3 in T Cells

AUTOR(ES)

Lund, Troy C.

FONTE

American Society for Microbiology

RESUMO

Constitutive activation of signal transducers and activators of transcription (STATs) has been associated with oncogenesis. Previously, a protein required for T-cell transformation by the DNA tumor virus herpesvirus saimiri (HVS) strain 484, designated tyrosine kinase-interacting protein (Tip-484), was shown to interact with and dramatically upregulate the activity of the STATs in an Lck-dependent manner. The minimal region of Tip-484 responsible for binding Lck was defined as a 10-residue C-terminal Src-related kinase homology domain, an 18-amino-acid spacer, and a 10-residue potential SH3 binding domain. This region is termed the LBD (for Lck binding domain). The present data show that only the LBD of Tip-484 is needed to activate Lck in vitro and in vivo. Finally, the LBD was shown to form a complex with STAT3 in vitro, and expression of the LBD in T cells led to STAT3 activation equal to that of full-length Tip-484. These studies demonstrate that the 48-amino-acid LBD of Tip-484 can perform as effectively as the full-length protein in vitro and in vivo.

Documentos Relacionados

• Activation of STAT transcription factors by herpesvirus Saimiri Tip-484 requires p56lck.
• Herpesvirus saimiri Tip-484 membrane protein markedly increases p56lck activity in T cells.
• Activation of Stat3 Transcription Factor by Herpesvirus Saimiri STP-A Oncoprotein
• Mutation of the Lck-Binding Motif of Tip Enhances Lymphoid Cell Activation by Herpesvirus Saimiri
• Downregulation of Lck-mediated signal transduction by tip of herpesvirus saimiri.