title: A putative sirolimus (rapamycin) effector protein.
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.
authors.affiliation: Department of Chemistry, Columbia University, New York, NY 10027.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.forename: A E
authors.initials: AE
authors.lastname: Rhoad
authors.forename: L
authors.initials: L
authors.lastname: Warner
authors.forename: T J
authors.initials: TJ
authors.lastname: Caggiano
authors.forename: A
authors.initials: A
authors.lastname: Failli
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: C L
authors.initials: CL
authors.lastname: Hsiao
authors.forename: K
authors.initials: K
authors.lastname: Nakanishi
authors.forename: K L
authors.initials: KL
authors.lastname: Molnar-Kimber
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism; D001483:Base Sequence; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D017931:DNA Primers; D005982:Glutathione Transferase / Q000302:isolation & purification; D006360:Heat-Shock Proteins / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011090:Polyenes / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D020123:Sirolimus; D013601:T-Lymphocytes / Q000378:metabolism*; D016559:Tacrolimus / Q000378:metabolism*; D022021:Tacrolimus Binding Proteins; D014407:Tumor Cells, Cultured
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; D006360:Heat-Shock Proteins; D007166:Immunosuppressive Agents; D011090:Polyenes; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D005982:Glutathione Transferase; D022021:Tacrolimus Binding Proteins; D020123:Sirolimus; D016559:Tacrolimus