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J. Biol. Chem., Vol. 275, Issue 22, 16574-16578, June 2, 2000
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From the Department of Immunology, The Lerner Research Institute,
The Cleveland Clinic Foundation, Cleveland, Ohio 44195
The Stat1 transcription factor plays a pivotal
role in both, the antiviral and antigrowth actions of interferons.
Stat1 acquires the ability to bind DNA by becoming phosphorylated on
Tyr701. However, to effectively stimulate gene
transcription, it must also be phosphorylated on Ser727. We
show that engagement of T cell antigen receptor (TCR)/CD3 complex in
either Jurkat cells or peripheral blood lymphocytes stimulates
phosphorylation of Ser727 but not Tyr701 of
Stat1. This process does not require the expression of tyrosine kinases
Lck and Zap-70. Interestingly, pretreatment of T cells with the Src
kinase inhibitor PP1 completely abrogated CD3-mediated serine
phosphorylation of Stat1, whereas inhibitors to MEK1 and phosphatidylinositol 3-kinase had no effect. Phosphorylation of Ser727 of Stat1 in T cells is not restricted to TCR/CD3 but
also results when cells are stimulated via the costimulatory molecule
CD28. The combination of CD3 and CD28 did not augment phosphorylation of Stat1 Ser727. Surprisingly, Stat1-mediated
transcriptional activity in response to IFN-
Signaling via the T Cell Antigen Receptor Induces Phosphorylation
of Stat1 on Serine 727*
and
was enhanced with CD3
stimulation, whereas CD3 alone had little effect. These findings
suggest that Stat1 is a signaling molecule in TCR signaling and may
play a role in T cell function.
*
This work was supported by National Institutes of Health
Grants CA77741 and CA77736 (to A. C. L.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Recipient of a National Research Service Award from the National
Institutes of Health.
§
To whom correspondence should be addressed: Dept. of
Immunology, Lerner Research Inst., NB-30, Cleveland Clinic Foundation, Cleveland, OH 44195. Tel.: 216-445-9045; Fax: 216-444-8372; E-mail: larnera@ccf.org.
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