Abstract
Sirolimus (rapamycin), a new immunosuppressive drug, inhibits proliferation of a wide spectrum of T and B cells. The immunosuppressive mechanism of sirolimus is still unclear. We recently isolated a membrane associated protein with an apparent molecular weight of 210 kDa, p210, from cultured Molt 4 cells and BJAB cells and from normal human T cells using an affinity matrix method. The p210 binds to sirolimus:FKBP12 complex, but only at background levels to FKBP12 alone, to FK506:FKBP12 complex, or sirolimus-biotin alone. Among the sirolimus analogs tested, the binding ability of p210 to drug:FKBP12 complexes correlates with the immunosuppressive activity of the drugs, suggesting that p210 is the sirolimus effector protein.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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B-Lymphocytes / metabolism
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Base Sequence
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Carrier Proteins / isolation & purification
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Carrier Proteins / metabolism*
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Cell Line
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Cells, Cultured
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Chromatography, Affinity
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DNA Primers
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Glutathione Transferase / isolation & purification
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Heat-Shock Proteins / isolation & purification
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Heat-Shock Proteins / metabolism*
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Humans
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Immunosuppressive Agents / metabolism*
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Molecular Sequence Data
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Molecular Weight
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Polyenes / metabolism*
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Polymerase Chain Reaction
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Recombinant Fusion Proteins / isolation & purification
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Recombinant Proteins / isolation & purification
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Recombinant Proteins / metabolism
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Sirolimus
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T-Lymphocytes / metabolism*
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Tacrolimus / metabolism*
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Tacrolimus Binding Proteins
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Tumor Cells, Cultured
Substances
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Carrier Proteins
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DNA Primers
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Heat-Shock Proteins
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Immunosuppressive Agents
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Polyenes
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Recombinant Fusion Proteins
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Recombinant Proteins
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Glutathione Transferase
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Tacrolimus Binding Proteins
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Sirolimus
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Tacrolimus