Immunophilins in protein folding and immunosuppression.
Lymphocyte activation requires the transmission of signals from molecules at the plasma membrane to nuclear signals that regulate gene expression. In recent years, several immunosuppressive compounds have been used as probes to identify important and potentially novel molecules involved in lymphocyte signal transduction processes. The immunosuppressants cyclosporin A (CsA), FK506, and rapamycin have been studied in particular detail. Two distinct classes of immunosuppressant binding proteins have been identified, and collectively termed immunophilins. The cyclophilin family of immunophilins binds CsA, whereas the FK506-binding protein (FKBP) family binds FK506 and rapamycin. This review will discuss both the endogenous functions of immunophilins as well as their roles in mediating immunosuppression.
Fruman
D A
DA
Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Burakoff
S J
SJ
Bierer
B E
BE
D000591:Amino Acid Isomerases / Q000737:chemistry / Q000502:physiology*; D000818:Animals; D019703:Calcineurin; D002148:Calmodulin-Binding Proteins / Q000502:physiology; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D016572:Cyclosporine / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D007108:Immune Tolerance; D019696:Peptidylprolyl Isomerase; D010749:Phosphoprotein Phosphatases / Q000502:physiology; D011090:Polyenes / Q000494:pharmacology; D017510:Protein Folding; D020123:Sirolimus; D016559:Tacrolimus / Q000494:pharmacology; D022021:Tacrolimus Binding Proteins
D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins; D006360:Heat-Shock Proteins; D011090:Polyenes; D016572:Cyclosporine; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D000591:Amino Acid Isomerases; D022021:Tacrolimus Binding Proteins; D019696:Peptidylprolyl Isomerase; D020123:Sirolimus; D016559:Tacrolimus