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.
Imbert
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Swiss Institute for Experimental Cancer Research (ISREC), Epalinges/Lausanne, Switzerland. Veronique.Imbert@isrec.unil.ch
Renauld
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D000818:Animals; D016207:Cytokines / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004789:Enzyme Activation; D004921:Erythropoietin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D006822:Hybrid Cells; D007376:Interleukin-2 / Q000494:pharmacology; D016906:Interleukin-9 / Q000494:pharmacology; D008223:Lymphoma; D051379:Mice; D008894:Milk Proteins; D051381:Rats; D017467:Receptors, Erythropoietin / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000235:genetics*; D053651:Receptors, Interleukin-9; D011994:Recombinant Proteins / Q000096:biosynthesis; D050799:STAT5 Transcription Factor; D013602:T-Lymphocytes, Cytotoxic; D013953:Thymus Neoplasms; D015534:Trans-Activators / Q000378:metabolism*; D014162:Transfection; D014638:Vanadates / Q000494:pharmacology
D016207:Cytokines; D004268:DNA-Binding Proteins; C508447:Il9r protein, rat; D007376:Interleukin-2; D016906:Interleukin-9; D008894:Milk Proteins; D017467:Receptors, Erythropoietin; D018123:Receptors, Interleukin; D015375:Receptors, Interleukin-2; D053651:Receptors, Interleukin-9; D011994:Recombinant Proteins; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D004921:Erythropoietin; D014638:Vanadates