Distinct roles for STAT1, STAT3, and STAT5 in differentiation gene induction and apoptosis inhibition by interleukin-9

Interleukin-9 (IL-9) activates three distinct STAT proteins: STAT1, STAT3, and STAT5. This process depends on one tyrosine of the n-9 receptor, which is necessary for proliferation, gene induction, and inhibition of apoptosis induced by glucocorticoids. By introduction of point mutations in amino ac ids surrounding this tyrosine, we obtained receptors that activated either STAT5 alone or both STAT1 and STAT3, thus providing us with the possibility to study the respective roles of these factors in the biological activitie s of IL-9. Both mutant receptors were able to prevent apoptosis, but only t he mutant that activated STAT1 and STAT3 was able to support induction of g ranzyme A and L-selectin. In line with these results, constitutively activa ted STATE blocked glucocorticoid-induced apoptosis. In Ba/F3 cells, signifi cant proliferation and pim-1 induction were observed with both STAT-restric ted mutants, though proliferation was lower than with the wild-type recepto r. These results suggest that survival and cell growth are redundantly cont rolled by multiple STAT factors, whereas differentiation gene induction is more specifically correlated with individual STAT activation by IL-9.