A putative sirolimus (rapamycin) effector protein.
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.
Chen
Y
Y
Department of Chemistry, Columbia University, New York, NY 10027.
Chen
H
H
Rhoad
A E
AE
Warner
L
L
Caggiano
T J
TJ
Failli
A
A
Zhang
H
H
Hsiao
C L
CL
Nakanishi
K
K
Molnar-Kimber
K L
KL
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
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