Molecular cloning and overexpression of the human FK506-binding protein FKBP.
The potent immunosuppressive agent FK506 is highly effective in preventing organ transplant rejection in humans. Like cyclosporin A, FK506 inhibits the transcription of early T-cell activation genes, apparently by modulating the activity of transcriptional regulators such as nuclear factor of activated T cells. A remarkable finding is that the predominant binding proteins (immunophilins) for cyclosporin A and FK506, cyclophilin and FKBP respectively, are peptidyl-prolyl-cis-trans-isomerases that are potently and selectively inhibited by their respective ligands. Here we report the complementary DNA and derived amino-acid sequences of human FKBP from Jurkat cells and also the efficient overexpression in Escherichia coli of fully active, recombinant human FKBP. The human FKBP cDNA sequence shows significant similarity to an open reading frame in the Neisseria meningitidis genome.
Department of Chemistry, Harvard University, Cambridge, Massachusetts 02138.
R F
RF
Standaert
A
A
Galat
G L
GL
Verdine
S L
SL
Schreiber
D000591:Amino Acid Isomerases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism*; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000235:genetics; D019696:Peptidylprolyl Isomerase; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D016559:Tacrolimus
D000900:Anti-Bacterial Agents; D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D004247:DNA; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase; D016559:Tacrolimus