Activation of STAT transcription factors by herpesvirus saimiri Tip-484 requires p56(lck)

Troy C. Lund, Roy Garcia, Maria M. Medveczky, Richard Jove, Peter G. Medveczky

Research output: Contribution to journalArticlepeer-review

86 Scopus citations

Abstract

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 p56(lck)· p56(lck) 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 p56(lck), and STAT3 was shown to be phosphorylated by the Tip-484-p56(lck) multiprotein complex in vitro. Infection oft 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 p56(lck) is required for STAT activation by Tip-484.

Original languageEnglish (US)
Pages (from-to)6677-6682
Number of pages6
JournalJournal of virology
Volume71
Issue number9
DOIs
StatePublished - 1997

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