Interleukin 2 induces a transient downregulation of protein phosphatase 1 and 2A activity in human T cells.
Stimulation of human CD4+ T cell lines with interleukin 2 (IL-2) induces tyrosine, serine and threonine phosphorylation of a series of proteins involved in the IL-2 receptor (IL-2R) signaling pathway. Here, we examined whether IL-2 induces changes in the activity of protein serine/threonine phosphatases in antigen specific, CD4+ human T cell lines. Using inhibitors of protein phosphatases 1 (PP1, PP2A, and PP2B, we provide evidence, that IL-2 induces a downregulation of PP activity in the cytoplasmic/membrane fraction. Thus, IL-2R ligation for 30 min triggers a 16 percent decrease in total PP2A activity (p < 0.0005, n = 17) and a seven percent decrease in PP1 activity (p < 0.00005, n = 17). Cytokine-induced downregulation of PP2A activity reaches a maximum 60 min after IL-2R ligation, and returns to baseline levels within two hours. Downregulation of PPI activity reaches a maximum after 30 min and is largely reversed one hour after IL-2 stimulation. As determined from immunoblotting experiments using a specific anti-PP1 or anti-PP2A antibody, the amount of PPI and PP2A recovered from cytosolic/membrane fraction remains unchanged after IL-2 treatment suggesting that the drop in PP1/PP2A activity might be due to a regulatory change rather than to a change in the amount of PP1 and PP2A. In conclusion, we provide evidence, for the first time, that IL-2 induces a transient downregulation of PP2A activity in T cells. In addition, our findings indicate that cytoplasmic PP1 activity is transiently downregulated following IL-2R ligation in antigen-specific, human CD4+ T cells.
Brockdorff
J
J
Institute of Medical Microbiology and Immunology, University of Copenhagen, Denmark.
Nielsen
M
M
Dobson
P
P
Geisler
C
C
Röpke
C
C
Svejgaard
A
A
Odum
N
N
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D002460:Cell Line; D015536:Down-Regulation; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D054645:Protein Phosphatase 1
D007376:Interleukin-2; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1