Abstract
Nuclear factor of activated T cells (NFAT) plays a key role in T cell activation. The activation of NFAT involves calcium- and calcineurin-dependent dephosphorylation and nuclear translocation from the cytoplasm, a process that is opposed by protein kinases. We show here that the peptidyl prolyl cis-trans isomerase Pin1 interacts specifically with the phosphorylated form of NFAT. The NFAT-Pin1 interaction is mediated through the WW domain of Pin1 and the serine-proline-rich domains of NFAT. Furthermore, binding of Pin1 to NFAT inhibits the calcineurin-mediated dephosphorylation of NFAT in vitro, and overexpression of Pin1 in T cells inhibits calcium-dependent activation of NFAT in vivo. These results suggest a possible role for Pin1 in the regulation of NFAT in T cells.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Motifs
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Blotting, Western
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Calcineurin / metabolism
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Calcium / metabolism*
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DNA-Binding Proteins / chemistry*
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DNA-Binding Proteins / metabolism*
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Doxycycline / pharmacology
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Glutathione Transferase / metabolism
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Humans
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Ionomycin / pharmacology
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Jurkat Cells
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Lymphocyte Activation
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NFATC Transcription Factors
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NIMA-Interacting Peptidylprolyl Isomerase
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Nuclear Proteins*
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Peptidylprolyl Isomerase / metabolism*
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Phosphorylation
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Plasmids / metabolism
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Proline / chemistry
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Protein Binding
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Protein Biosynthesis
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Protein Structure, Tertiary
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Serine / chemistry
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Tetradecanoylphorbol Acetate / pharmacology
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Transcription Factors / chemistry*
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Transcription Factors / metabolism*
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Transcription, Genetic
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Transfection
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cis-trans-Isomerases / chemistry*
Substances
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DNA-Binding Proteins
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NFATC Transcription Factors
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NIMA-Interacting Peptidylprolyl Isomerase
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Nuclear Proteins
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Transcription Factors
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Serine
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Ionomycin
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Proline
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Glutathione Transferase
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Calcineurin
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cis-trans-Isomerases
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PIN1 protein, human
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Peptidylprolyl Isomerase
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Doxycycline
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Tetradecanoylphorbol Acetate
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Calcium