The immunophilins are a highly conserved family of cis-trans peptidyl-prolyl isomerases that bind to and mediate the effects of immunosuppressive drugs, such as cyclosporin, FK506 and rapamycin. Several related immunophilins, FKBP12, FKBP51 and FKBP52, are characterized as cytosolic FK506-binding proteins, and following ligand binding, they functionally inhibit the phosphatase activity of calcineurin. The ubiquitously expressed FKBP12 also associates with the cytoplasmic domain of the TGFβ-type I receptor, where it stabilizes the inactive conformation of the receptor and blocks the activation of the TGFβ pathway. FKBP51 and FKBP52 are two highly related proteins. FKBP51 is predominantly expressed in T cells and is induced by glucocorticoids. FKBP51 mediates the effects of FK506 and rapamycin by inhibiting intracellular calcineurin activity, and by blocking T-cell activation and proliferation. FKBP52, known also as FKBP-59 or heat shock protein 56, is expressed in a variety of tissues and can also associate with the heat shock protein (hsp90) in mature steroid receptor complexes (6,8).
