Immunosuppressive drugs prevent a rapid dephosphorylation of transcription factor NFAT1 in stimulated immune cells

Karen T.Y. Shaw; Andrew M. Ho; Anuradha Raghavan; Jaime Kim; Jugnu Jain; Jungchan Park; Surendra Sharma; Anjana Rao; Patrick G. Hogan

doi:10.1073/pnas.92.24.11205

Immunosuppressive drugs prevent a rapid dephosphorylation of transcription factor NFAT1 in stimulated immune cells

Karen T.Y. Shaw, Andrew M. Ho, Anuradha Raghavan, Jaime Kim, Jugnu Jain, Jungchan Park, Surendra Sharma, Anjana Rao, Patrick G. Hogan

Research output: Contribution to journal › Article › peer-review

Abstract

The immunosuppressive drugs cyclosporin A and FK506 interfere with the inducible transcription of cytokine genes in T cells and in other immune cells, in part by preventing the activation of NF-AT (nuclear factor of activated T cells). We show that transcription factor NFAT1 in T cells is rapidly dephosphorylated on stimulation, that dephosphorylation occurs before translocation of NFAT1 into the cell nucleus, and that dephosphorylation increases the affinity of NFAT1 for its specific sites in DNA. Cyclosporin A prevents the dephosphorylation and the nuclear translocation of NFAT1 in T cells, B cells, macrophages, and mast cells, delineating at least one mechanism that contributes to the profound immunosuppressive effects of this compound.

Original language	English (US)
Pages (from-to)	11205-11209
Number of pages	5
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	92
Issue number	24
DOIs	https://doi.org/10.1073/pnas.92.24.11205
State	Published - Nov 21 1995
Externally published	Yes

Keywords

DNA binding
FK506
cyclosporin A
nuclear translocation

ASJC Scopus subject areas

General

Access to Document

10.1073/pnas.92.24.11205

Cite this

Shaw, K. T. Y., Ho, A. M., Raghavan, A., Kim, J., Jain, J., Park, J., Sharma, S., Rao, A., & Hogan, P. G. (1995). Immunosuppressive drugs prevent a rapid dephosphorylation of transcription factor NFAT1 in stimulated immune cells. Proceedings of the National Academy of Sciences of the United States of America, 92(24), 11205-11209. https://doi.org/10.1073/pnas.92.24.11205

Immunosuppressive drugs prevent a rapid dephosphorylation of transcription factor NFAT1 in stimulated immune cells. / Shaw, Karen T.Y.; Ho, Andrew M.; Raghavan, Anuradha et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, No. 24, 21.11.1995, p. 11205-11209.

Research output: Contribution to journal › Article › peer-review

@article{28b431ec74b5408396d0220b2388380f,

title = "Immunosuppressive drugs prevent a rapid dephosphorylation of transcription factor NFAT1 in stimulated immune cells",

abstract = "The immunosuppressive drugs cyclosporin A and FK506 interfere with the inducible transcription of cytokine genes in T cells and in other immune cells, in part by preventing the activation of NF-AT (nuclear factor of activated T cells). We show that transcription factor NFAT1 in T cells is rapidly dephosphorylated on stimulation, that dephosphorylation occurs before translocation of NFAT1 into the cell nucleus, and that dephosphorylation increases the affinity of NFAT1 for its specific sites in DNA. Cyclosporin A prevents the dephosphorylation and the nuclear translocation of NFAT1 in T cells, B cells, macrophages, and mast cells, delineating at least one mechanism that contributes to the profound immunosuppressive effects of this compound.",

keywords = "DNA binding, FK506, cyclosporin A, nuclear translocation",

author = "Shaw, {Karen T.Y.} and Ho, {Andrew M.} and Anuradha Raghavan and Jaime Kim and Jugnu Jain and Jungchan Park and Surendra Sharma and Anjana Rao and Hogan, {Patrick G.}",

year = "1995",

month = nov,

day = "21",

doi = "10.1073/pnas.92.24.11205",

language = "English (US)",

volume = "92",

pages = "11205--11209",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "24",

}

TY - JOUR

T1 - Immunosuppressive drugs prevent a rapid dephosphorylation of transcription factor NFAT1 in stimulated immune cells

AU - Shaw, Karen T.Y.

AU - Ho, Andrew M.

AU - Raghavan, Anuradha

AU - Kim, Jaime

AU - Jain, Jugnu

AU - Park, Jungchan

AU - Sharma, Surendra

AU - Rao, Anjana

AU - Hogan, Patrick G.

PY - 1995/11/21

Y1 - 1995/11/21

N2 - The immunosuppressive drugs cyclosporin A and FK506 interfere with the inducible transcription of cytokine genes in T cells and in other immune cells, in part by preventing the activation of NF-AT (nuclear factor of activated T cells). We show that transcription factor NFAT1 in T cells is rapidly dephosphorylated on stimulation, that dephosphorylation occurs before translocation of NFAT1 into the cell nucleus, and that dephosphorylation increases the affinity of NFAT1 for its specific sites in DNA. Cyclosporin A prevents the dephosphorylation and the nuclear translocation of NFAT1 in T cells, B cells, macrophages, and mast cells, delineating at least one mechanism that contributes to the profound immunosuppressive effects of this compound.

AB - The immunosuppressive drugs cyclosporin A and FK506 interfere with the inducible transcription of cytokine genes in T cells and in other immune cells, in part by preventing the activation of NF-AT (nuclear factor of activated T cells). We show that transcription factor NFAT1 in T cells is rapidly dephosphorylated on stimulation, that dephosphorylation occurs before translocation of NFAT1 into the cell nucleus, and that dephosphorylation increases the affinity of NFAT1 for its specific sites in DNA. Cyclosporin A prevents the dephosphorylation and the nuclear translocation of NFAT1 in T cells, B cells, macrophages, and mast cells, delineating at least one mechanism that contributes to the profound immunosuppressive effects of this compound.

KW - DNA binding

KW - FK506

KW - cyclosporin A

KW - nuclear translocation

UR - http://www.scopus.com/inward/record.url?scp=0028885878&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028885878&partnerID=8YFLogxK

U2 - 10.1073/pnas.92.24.11205

DO - 10.1073/pnas.92.24.11205

M3 - Article

C2 - 7479966

AN - SCOPUS:0028885878

SN - 0027-8424

VL - 92

SP - 11205

EP - 11209

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 24

ER -

Immunosuppressive drugs prevent a rapid dephosphorylation of transcription factor NFAT1 in stimulated immune cells

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this