Recruitment of Stat4 to the Human Interferon-α/β Receptor Requires Activated Stat2

J. David Farrar, Janice D. Smith, Theresa L. Murphy, Kenneth M. Murphy
2000 Journal of Biological Chemistry  
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)-␣ 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
more » ... 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 Stat2deficient 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.
doi:10.1074/jbc.275.4.2693 pmid:10644731 fatcat:fgegzr3hcbcjhmjqrquq3gy2fe