Protein phosphatase 2A (PP2A) regulates interleukin-4-mediated STAT6 signaling
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Protein phosphatase 2A (PP2A) regulates interleukin-4-mediated STAT6 signaling. / Woetmann, Anders; Brockdorff, Johannes; Lovato, Paola; Nielsen, Mette; Leick, Vagn; Rieneck, Klaus; Svejgaard, Arne; Geisler, Carsten; Ødum, Niels.
In: Journal of Biological Chemistry, Vol. 278, No. 5, 2002, p. 2787-91.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Protein phosphatase 2A (PP2A) regulates interleukin-4-mediated STAT6 signaling
AU - Woetmann, Anders
AU - Brockdorff, Johannes
AU - Lovato, Paola
AU - Nielsen, Mette
AU - Leick, Vagn
AU - Rieneck, Klaus
AU - Svejgaard, Arne
AU - Geisler, Carsten
AU - Ødum, Niels
N1 - Keywords: Base Sequence; CD4-Positive T-Lymphocytes; Cell Line; Enzyme Inhibitors; Humans; Interleukin-4; Jurkat Cells; Molecular Sequence Data; Oligodeoxyribonucleotides; Oxazoles; Phosphoprotein Phosphatases; Phosphorylation; Promoter Regions (Genetics); Protein Phosphatase 2; Recombinant Proteins; STAT6 Transcription Factor; Signal Transduction; Staurosporine; Trans-Activators; Transfection
PY - 2002
Y1 - 2002
N2 - Interleukin-4 (IL-4) plays a pivotal role in the induction and maintenance of allergy by promoting Th2 differentiation and B cell isotype switching to IgE. Studies on STAT6-deficient mice have demonstrated the essential role of STAT6 in mediating the biological functions of IL-4. IL-4 induces tyrosine phosphorylation of STAT6, which in turn leads to transcription of IL-4-specific genes. In addition, serine phosphorylation of STAT6 has recently been reported. Here we study the functional role of STAT6 serine phosphorylation and the kinases and phosphatases involved. We show that inhibition of protein phosphatase 2A (PP2A) induces serine phosphorylation of STAT6 and severely inhibits DNA binding of STAT6. In contrast, IL-4-induced tyrosine phosphorylation of Janus kinase-1 and STAT6 is not affected, suggesting that PP2A acts downstream of Janus kinases in IL-4 signaling. In conclusion, we provide the first evidence that PP2A plays a crucial role in the regulation of STAT6 function.
AB - Interleukin-4 (IL-4) plays a pivotal role in the induction and maintenance of allergy by promoting Th2 differentiation and B cell isotype switching to IgE. Studies on STAT6-deficient mice have demonstrated the essential role of STAT6 in mediating the biological functions of IL-4. IL-4 induces tyrosine phosphorylation of STAT6, which in turn leads to transcription of IL-4-specific genes. In addition, serine phosphorylation of STAT6 has recently been reported. Here we study the functional role of STAT6 serine phosphorylation and the kinases and phosphatases involved. We show that inhibition of protein phosphatase 2A (PP2A) induces serine phosphorylation of STAT6 and severely inhibits DNA binding of STAT6. In contrast, IL-4-induced tyrosine phosphorylation of Janus kinase-1 and STAT6 is not affected, suggesting that PP2A acts downstream of Janus kinases in IL-4 signaling. In conclusion, we provide the first evidence that PP2A plays a crucial role in the regulation of STAT6 function.
U2 - 10.1074/jbc.M210196200
DO - 10.1074/jbc.M210196200
M3 - Journal article
C2 - 12426308
VL - 278
SP - 2787
EP - 2791
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 5
ER -
ID: 8544491