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

328 Scopus citations

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

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10.1073/pnas.92.24.11205

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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

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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.

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

Abstract

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