Activation of STAT transcription factors by herpesvirus Saimiri Tip-484 requires p56lck.

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 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.

journal_name

J Virol

journal_title

Journal of virology

authors

Lund TC,Garcia R,Medveczky MM,Jove R,Medveczky PG

doi

10.1128/JVI.71.9.6677-6682.1997

subject

Has Abstract

pub_date

1997-09-01 00:00:00

pages

6677-82

issue

9

eissn

0022-538X

issn

1098-5514

journal_volume

71

pub_type

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