A PUTATIVE SIROLIMUS (RAPAMYCIN) EFFECTOR PROTEIN

Sirolimus (rapamycin), a new immunosuppressive drug, inhibits prolifer ation of a wide spectrum of T and B cells. The immunosuppressive mecha nism of sirolimus is still unclear. We recently isolated a membrane as sociated protein with an apparent molecular weight of 210 kDa, p210, f rom cultured Molt 4 cells and BJAB cells and from normal human T cells using an affinity matrix method. The p210 binds to sirolimus:FKBP12 c omplex, but only at background levels to FKBP12 alone, to FK506:FKBP12 complex, or sirolimus-biotin alone. Among the sirolimus analogs teste d, the binding ability of p210 to drug:FKBP12 complexes correlates wit h the immunosuppressive activity of the drugs, suggesting that p210 is the sirolimus effector protein. (C) 1994 Academic Press, Inc.