The immunosuppressant FK-506, like cyclosporins and didemnin B, inhibits calmodulin-dependent phosphorylation of the elongation factor 2 in vitro and biological effects of the phorbol ester TPA on mouse skin in vivo.
Similar to previous observations with cyclosporins and didemnin B, the novel immunosuppressant FK-506 inhibits the Ca2+/calmodulin-dependent phosphorylation of the eukaryotic elongation factor 2 of protein synthesis in vitro and biological effects of the phorbol ester TPA on mouse skin in vivo. These effects include the induction of the ear edema and the stimulation of alkaline phosphatase activity. FK-506 neither activates nor inhibits protein kinase C in vitro. FK-506 does not compete with cyclosporin A for the high-affinity binding sites in mouse epidermis cytosol.
Gschwendt
M
M
Department of Biochemistry, German Cancer Research Center, Heidelberg.
Kittstein
W
W
Marks
F
F
D000818:Animals; D001665:Binding Sites; D002147:Calmodulin / Q000378:metabolism; D003524:Cyclosporins / Q000378:metabolism / Q000494:pharmacology; D047630:Depsipeptides; D005260:Female; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D020652:Peptide Elongation Factor 2; D010445:Peptide Elongation Factors / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000494:pharmacology; D010766:Phosphorylation; D011725:Pyridines / Q000378:metabolism / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D016559:Tacrolimus; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors*
D002147:Calmodulin; D003524:Cyclosporins; D047630:Depsipeptides; D007166:Immunosuppressive Agents; D020652:Peptide Elongation Factor 2; D010445:Peptide Elongation Factors; D010456:Peptides, Cyclic; D011725:Pyridines; C030051:didemnins; D013755:Tetradecanoylphorbol Acetate; D016559:Tacrolimus