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Journal of Virology, February 1999, p. 1689-1694, Vol. 73, No. 2
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.
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
*
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.
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