The mechanism of action of the immunosuppressive drug FK-506.
The novel immunosuppressive drug FK-506 inhibits the induction of lymphocyte proliferation in vitro by mitogenic combinations of phorbol esters and calcium ionophores. Early events inducible by phorbol esters alone are unaffected, while changes induced by calcium ionophores alone are completely suppressed by as little as 0.1 nM FK-506. The event in lymphocyte activation inhibited by FK-506 is completed early in the response. Its completion requires the provision of a Ca2+ signal and concurrent activation of protein kinase C and is accelerated as a function of the strength of protein kinase C activation.
Kay
J E
JE
Biochemistry Laboratory, School of Biological Sciences, University of Sussex, Brighton, United Kingdom.
Doe
S E
SE
Benzie
C R
CR
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D003524:Cyclosporins / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D011493:Protein Kinase C / Q000502:physiology; D013552:Swine; D016559:Tacrolimus; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D003524:Cyclosporins; D007166:Immunosuppressive Agents; D000001:Calcimycin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D016559:Tacrolimus