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Journal of Virology, February 1999, p. 1689-1694, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

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

Troy C. Lund, Paul C. Prator, Maria M. Medveczky, and Peter G. Medveczky*

Department of Medical Microbiology and Immunology, Institute for Biomolecular Science, and the H. Lee Moffit Cancer Center and Research Institute, University of South Florida, Tampa, Florida 33612-4799

Received 10 August 1998/Accepted 5 November 1998

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.

* Corresponding author. Mailing address: Dept. of Medical Microbiology and Immunology, University of South Florida, MDC 10, 12901 Bruce B. Downs Blvd., Tampa, FL 33612. Phone: (813) 974-2372. Fax: (813) 974-4151. E-mail: pmedvecz{at}com1.med.usf.edu.

Journal of Virology, February 1999, p. 1689-1694, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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