Interleukin 2 induces a transient downregulation of protein phosphatase 1 and 2A activity in human T cells

J Brockdorff; M Nielsen; P Dobson; C Geisler; C Röpke; A Svejgaard; N Odum

Interleukin 2 induces a transient downregulation of protein phosphatase 1 and 2A activity in human T cells

J Brockdorff, M Nielsen, P Dobson, C Geisler, C Röpke, A Svejgaard, N Odum

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Abstract

Udgivelsesdato: 1997-Mar

Originalsprog	Engelsk
Tidsskrift	HLA
Vol/bind	49
Udgave nummer	3 Pt 1
Sider (fra-til)	228-35
Antal sider	7
ISSN	2059-2302
Status	Udgivet - 1997

Bibliografisk note

Keywords: CD4-Positive T-Lymphocytes; Cell Line; Down-Regulation; Humans; Interleukin-2; Phosphoprotein Phosphatases; Protein Phosphatase 1

Citationsformater

@article{3517af60b0a511ddb538000ea68e967b,

title = "Interleukin 2 induces a transient downregulation of protein phosphatase 1 and 2A activity in human T cells",

abstract = "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.",

author = "J Brockdorff and M Nielsen and P Dobson and C Geisler and C R{\"o}pke and A Svejgaard and N Odum",

note = "Keywords: CD4-Positive T-Lymphocytes; Cell Line; Down-Regulation; Humans; Interleukin-2; Phosphoprotein Phosphatases; Protein Phosphatase 1",

year = "1997",

language = "English",

volume = "49",

pages = "228--35",

journal = "HLA",

issn = "2059-2302",

publisher = "Wiley",

number = "3 Pt 1",

}

TY - JOUR

T1 - Interleukin 2 induces a transient downregulation of protein phosphatase 1 and 2A activity in human T cells

AU - Brockdorff, J

AU - Nielsen, M

AU - Dobson, P

AU - Geisler, C

AU - Röpke, C

AU - Svejgaard, A

AU - Odum, N

N1 - Keywords: CD4-Positive T-Lymphocytes; Cell Line; Down-Regulation; Humans; Interleukin-2; Phosphoprotein Phosphatases; Protein Phosphatase 1

PY - 1997

Y1 - 1997

N2 - 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.

AB - 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.

M3 - Journal article

C2 - 9098929

SN - 2059-2302

VL - 49

SP - 228

EP - 235

JO - HLA

JF - HLA

IS - 3 Pt 1

ER -