Duration of STAT5 activation influences the response of interleukin-2 receptor alpha gene to different cytokines.

Cytokines and growth factors regulate expression of their target genes via the Janus kinase (Jak)/signal transducers and activators of transcription (STAT) signaling pathway. One of the best characterized targets of STAT is the interleukin-2 receptor-alpha (IL-2Ralpha) gene. Its transcription is controlled by interleukin 2 (IL-2) through STAT5 activation. Using the PC60 cell line, in which the role of STAT5 in the regulation of the murine IL-2Ralpha gene by IL-2 has been elucidated, we have compared the response of this gene to IL-2, interleukin-9 (IL-9) and erythropoietin (Epo). IL-2 and IL-9, but not Epo, stimulate cell surface expression of IL-2Ralpha. This correlates with the fact that IL-2 and IL-9 support long-term STAT5 activation whereas Epo only induces transient activation. In cells treated with vanadate, a protein tyrosine phosphatase (PTP) inhibitor, Epo induces prolonged STAT5 activation and strongly stimulates IL-2Ralpha expression. Our study suggests that by controlling the duration of the STAT activation signal, PTP influences the specificity of cytokine signaling.