Interleukin 2 and 15 activate Stat3alpha in human T lymphocytes.
Signal transducer and activator of transcription 3 (Stat3) has recently been shown to exist in two alternatively spliced isoforms, a short form, Stat3beta, and a longer form, Stat3alpha, displaying differences in transcriptional activity. It is unknown which Stat3 isoform(s) is activated in response to interleukin (IL)-2 and IL-15. Here, cytokine-induced activation of Stat3 in previously activated CD4(+) human T cells was examined using Stat3 antibodies directed against different regions of Stat3. As determined by tyrosine phosphorylation, nuclear translocation and binding to an hSIE-oligonucleotide probe, IL-2 and IL-15 activated the slowly migrating isoform, Stat3alpha. In contrast, minimal or no activation of Stat3beta was observed, suggesting that IL-2 and IL-15 predominantly activate Stat3alpha in human CD4(+) T cells. In this way, diversity in the expression and activation of Stat3 proteins may provide additional means of regulating cytokine-induced T cell responses.
Nielsen
M
M
Institute of Medical Microbiology and Immunology, University of Copenhagen, Denmark. M.Nielsen@sb.immi.ku.dk
Nordahl
M
M
Svejgaard
A
A
Odum
N
N
D000209:Acute-Phase Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000737:chemistry; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D050796:STAT3 Transcription Factor; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D015534:Trans-Activators / Q000032:analysis / Q000378:metabolism*
D000209:Acute-Phase Proteins; D004268:DNA-Binding Proteins; D019409:Interleukin-15; D007376:Interleukin-2; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D004247:DNA; D011505:Protein-Tyrosine Kinases