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 t he interleukin-2 receptor-alpha (IL-2R alpha) gene. Its transcription is co ntrolled by interleukin 2 (IL-2) through STAT5 activation. Using the PC60 c ell line, in which the role of STAT5 in the regulation of the murine IL-2Ra gene by IL-2 has been elucidated, we have compared the response of this ge ne to IL-2, interleukin-9 (IL-9) and erythropoietin (Epo), IL-2 and IL-9, b ut not Epo, stimulate cell surface expression of IL-2R alpha. This correlat es with the fact that IL-2 and IL-9 support long-term STAT5 activation wher eas 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-2R alpha expression. Our study sugge sts that by controlling the duration of the STAT activation signal, PTP inf luences the specificity of cytokine signaling.