A cytosolic binding protein for the immunosuppressant FK506 has peptidyl-prolyl isomerase activity but is distinct from cyclophilin

John Siekierka, Shirley H.Y. Hung, Martin Poe, C. Shirley Lin, Nolan H. Sigal

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822 Citations (Scopus)

Abstract

CYCLOSPORIN A and the newly discovered immunosuppressant, FK-506, are potent inhibitors of T cell activation. In addition to their clinical importance in the prevention of allograft rejection, cyclosporin A and FK-506 represent important reagents for the study of the molecular mechanisms of lymphocyte activation. Cyclosporin A, a cyclic undecapeptide and FK-506, a macrolide, although chemically distinct, inhibit similar lymphocyte activation responses. The earliest responses inhibited in the T cell seem to be the expression of early phase T cell-activation genes for interleukins 2, 3 and 4, granulocyte-macrophage colony stimulating factor and gamma interferon. Although FK-506 and cyclosporin A seem to inhibit similar signal transduction processes, they do so by interacting with distinct cytosolic proteins. We report here the purification to homogeneity of a specific FK-506 binding protein that is distinct from the cyclosporin A-binding protein, cyclophilin. In addition, we show that this FK-506 binding protein, like cyclophilin, has peptidyl-prolyl isomerase activity.

Original languageEnglish
Pages (from-to)755-757
Number of pages3
JournalNature
Volume341
Issue number6244
DOIs
StatePublished - 1 Jan 1989

Fingerprint

Tacrolimus Binding Proteins
Peptidylprolyl Isomerase
Cyclophilins
Immunosuppressive Agents
Cyclosporine
Tacrolimus
Lymphocyte Activation
T-Lymphocytes
Interleukin-3
Macrolides
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-4
Transcriptional Activation
Interferon-gamma
Interleukin-2
Allografts
Signal Transduction
Proteins

Cite this

Siekierka, John ; Hung, Shirley H.Y. ; Poe, Martin ; Lin, C. Shirley ; Sigal, Nolan H. / A cytosolic binding protein for the immunosuppressant FK506 has peptidyl-prolyl isomerase activity but is distinct from cyclophilin. In: Nature. 1989 ; Vol. 341, No. 6244. pp. 755-757.
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abstract = "CYCLOSPORIN A and the newly discovered immunosuppressant, FK-506, are potent inhibitors of T cell activation. In addition to their clinical importance in the prevention of allograft rejection, cyclosporin A and FK-506 represent important reagents for the study of the molecular mechanisms of lymphocyte activation. Cyclosporin A, a cyclic undecapeptide and FK-506, a macrolide, although chemically distinct, inhibit similar lymphocyte activation responses. The earliest responses inhibited in the T cell seem to be the expression of early phase T cell-activation genes for interleukins 2, 3 and 4, granulocyte-macrophage colony stimulating factor and gamma interferon. Although FK-506 and cyclosporin A seem to inhibit similar signal transduction processes, they do so by interacting with distinct cytosolic proteins. We report here the purification to homogeneity of a specific FK-506 binding protein that is distinct from the cyclosporin A-binding protein, cyclophilin. In addition, we show that this FK-506 binding protein, like cyclophilin, has peptidyl-prolyl isomerase activity.",
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A cytosolic binding protein for the immunosuppressant FK506 has peptidyl-prolyl isomerase activity but is distinct from cyclophilin. / Siekierka, John; Hung, Shirley H.Y.; Poe, Martin; Lin, C. Shirley; Sigal, Nolan H.

In: Nature, Vol. 341, No. 6244, 01.01.1989, p. 755-757.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - A cytosolic binding protein for the immunosuppressant FK506 has peptidyl-prolyl isomerase activity but is distinct from cyclophilin

AU - Siekierka, John

AU - Hung, Shirley H.Y.

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AU - Sigal, Nolan H.

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AB - CYCLOSPORIN A and the newly discovered immunosuppressant, FK-506, are potent inhibitors of T cell activation. In addition to their clinical importance in the prevention of allograft rejection, cyclosporin A and FK-506 represent important reagents for the study of the molecular mechanisms of lymphocyte activation. Cyclosporin A, a cyclic undecapeptide and FK-506, a macrolide, although chemically distinct, inhibit similar lymphocyte activation responses. The earliest responses inhibited in the T cell seem to be the expression of early phase T cell-activation genes for interleukins 2, 3 and 4, granulocyte-macrophage colony stimulating factor and gamma interferon. Although FK-506 and cyclosporin A seem to inhibit similar signal transduction processes, they do so by interacting with distinct cytosolic proteins. We report here the purification to homogeneity of a specific FK-506 binding protein that is distinct from the cyclosporin A-binding protein, cyclophilin. In addition, we show that this FK-506 binding protein, like cyclophilin, has peptidyl-prolyl isomerase activity.

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