Activation of STAT transcription factors by herpesvirus Saimiri Tip-484 requires p56lck.
Signal transducers and activators of transcription (STATs) relay signals from activated cell surface receptors directly to the nucleus. Previously, a protein required for T-cell transformation by the DNA tumor virus herpesvirus saimiri (HVS) and designated tyrosine kinase interacting protein (Tip-484) was shown to interact with and dramatically upregulate the activity of p56lck. p56lck is a nonreceptor tyrosine kinase that is essential for signaling by the T-cell receptor and also interacts with the CD4, CD8, and interleukin-2 receptors. The present data show activation of STAT1 and -3 by Tip-484. STAT1 and -3 were also found to complex with glutathione S-transferase-Tip-484 only in the presence of p56lck, and STAT3 was shown to be phosphorylated by the Tip-484-p56lck multiprotein complex in vitro. Infection of T cells with HVS or expression of recombinant Tip-484 significantly increased the DNA-binding activity of the STAT1 and STAT3 transcription factors in nuclear extracts and also increased the phosphorylation of STAT3 in vivo. This is the first report of STAT activation by a DNA tumor virus protein. Moreover, these studies demonstrate that p56lck is required for STAT activation by Tip-484.
Lund
T C
TC
Department of Medical Microbiology and Immunology, University of South Florida, Tampa 33612-4799, USA.
Garcia
R
R
Medveczky
M M
MM
Jove
R
R
Medveczky
P G
PG
D000818:Animals; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006567:Herpesvirus 2, Saimiriine / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D013379:Substrate Specificity; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation; D015854:Up-Regulation; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D014764:Viral Proteins; C092384:tyrosine kinase interacting protein, Saimiriine herpesvirus 2; D004247:DNA; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases