Interleukin-2 induces tyrosine phosphorylation and nuclear translocation of stat3 in human T lymphocytes.
An early biochemical event associated with T cell activation through the interleukin-2 receptor (IL-2R) is tyrosine phosphorylation of several intracellular substrates. The exact mechanism by which IL-2 regulates transcription of different genes is presently unknown. Here, we report that stimulation through the IL-2R induced tyrosine phosphorylation and subsequent nuclear translocation of stat3, a newly identified member of the signal transducers and activators of transcription (STAT) family of proteins. In contrast, stat1 proteins were not tyrosine phosphorylated after IL-2 ligation, whereas tyrosine-phosphorylated stat1 proteins (91 and 84 kDa proteins) were translocated to the nucleus following interferon-gamma treatment of HeLa cells. Apart from stat3, another cytoplasmic protein was tyrosine phosphorylated and subsequently translocated to the nucleus in response to IL-2. This protein had an apparent molecular mass of 84 kDa and was not recognized by stat3 or stat1 mAb or antisera. Since IL-2 induced nuclear translocation of the 84 kDa protein and stat3 followed identical kinetics, p84 is a candidate for a new, yet undefined, member of the STAT family. Taken together, we report that IL-2 induces tyrosine phosphorylation and subsequent nuclear translocation of stat3 and an as yet undefined 84-kDa protein in antigen-specific human T cell lines.
Nielsen
M
M
Cell Cybernetics Laboratory, University of Copenhagen, Denmark.
Svejgaard
A
A
Skov
S
S
Odum
N
N
D001692:Biological Transport; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000378:metabolism; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D004268:DNA-Binding Proteins; D007376:Interleukin-2; D009687:Nuclear Proteins; D015375:Receptors, Interleukin-2; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases