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J Biol Chem, Vol. 275, Issue 4, 2693-2697, January 28, 2000
From the Department of Pathology and Center for Immunology, Howard
Hughes Medical Institute, Washington University School of Medicine,
St. Louis, Missouri 63110
Stat4 activation is involved in differentiation
of type 1 helper (Th1) T cells. Although Stat4 is activated by
interleukin (IL)-12 in both human and murine T cells, Stat4 is
activated by interferon (IFN)-
Recruitment of Stat4 to the Human Interferon-
/
Receptor
Requires Activated Stat2*
,
only in human, but not murine,
CD4+ T cells. This species-specific difference in
cytokine activation of Stat4 underlies critical differences in Th1
development in response to cytokines and is important to the
interpretation of murine models of immunopathogenesis. Here, we sought
to determine the mechanism of Stat4 recruitment and activation by the
human IFN- receptor. Analysis of phosphopeptide binding analysis
suggests that Stat4 does not interact directly with
tyrosine-phosphorylated amino acid residues within the cytoplasmic
domains of either of the subunits of the IFN- receptor complex.
Expression of murine Stat4 in the Stat1-deficient U3A and the
Stat2-deficient U6A cell lines shows that IFN--induced Stat4
phosphorylation requires the presence of activated Stat2 but not Stat1.
Thus, in contrast to the direct recruitment of Stat4 by the IL-12
receptor, Stat4 activation by the human IFN- receptor occurs through
indirect recruitment by intermediates involving Stat2.
*
This work was supported in part by National Institutes of
Health Grant AIDK39676 and a grant from the Juvenile Diabetes
Foundation.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.
Supported by Training Grant CA09547 in Cancer Biology from NCI,
National Institutes of Health.
§
An associate investigator of the Howard Hughes Medical Institute.
To whom correspondence should be addressed: Dept. of Pathology, Washington University School of Medicine, 660 S. Euclid Ave., St.
Louis, MO 63110. Tel.: 314-362-2009; Fax: 314-747-4888; E-mail: murphy@immunology.wustl.edu.
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