FK-506 and cyclosporin A: immunosuppressive mechanism of action and beyond.
Cyclosporin A and FK-506 are important therapeutic agents that have found widespread use in preventing graft rejection during tissue transplantation. Research efforts aimed at elucidating the molecular mechanism of action of these drugs have, in addition to defining their immunosuppressive functions, led to the identification of two new gene families whose products may function as components of several diverse signal transduction pathways. In the presence of the immunosuppressive drugs, some members of the receptor families interact with the Ca2+/calmodulin-dependent protein phosphatase 2B, also known as calcineurin. Inhibition of phosphatase activity may effect several downstream biochemical processes. In this way, cyclosporin A and FK-506 have proved to be useful probes of signaling events in both lymphocytic and other cell types.
Siekierka
J J
JJ
Department of Immunology Research, Merck Research Laboratories, Rahway, New Jersey 07065.
Sigal
N H
NH
D000591:Amino Acid Isomerases / Q000502:physiology; D000818:Animals; D019703:Calcineurin; D002148:Calmodulin-Binding Proteins / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology; D016572:Cyclosporine / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D008213:Lymphocyte Activation; D019696:Peptidylprolyl Isomerase; D010749:Phosphoprotein Phosphatases / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology; D016559:Tacrolimus / Q000494:pharmacology* / Q000633:toxicity; D022021:Tacrolimus Binding Proteins
D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins; D016572:Cyclosporine; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D000591:Amino Acid Isomerases; D022021:Tacrolimus Binding Proteins; D019696:Peptidylprolyl Isomerase; D016559:Tacrolimus