3 DISTINCT MESSENGER-RNAS CAN ENCODE THE HUMAN IMMUNOSUPPRESSANT-BINDING PROTEIN FKBP12

FKBP12 is an 11.8-kDa protein that binds the potent immunosuppressants FK506 and rapamycin. When bound to FK506, FKBP12 forms an inhibitory complex with calcineurin and interferes with signal transduction in ac tivated T lymphocytes. In studying human FKBP12 cDNAs and the human FK BP12 gene, we found that three distinct transcripts can encode human F KBP12. The transcripts, which we designate FKBP 12A, 12B and 12C, cont ain identical open reading frames, but vary in abundance and are disti nguished by unique 3' untranslated regions. The mature transcripts der ive from either four or five exons and are generated by the differenti al use of one splice junction and three cleavage-polyadenylation sites within FKBP12. FKBP12A and 12B populations increase in abundance and/ or stability when T-cell populations are mitogenically activated in vi tro, implying that one result of T-cell stimulation is increased deman d for the FKBP12 message. These transcripts are also present in a vari ety of human tissues, suggesting that FKBP12 and/or the mRNAs encoding it might affect physiological function(s) in a diverse array of cells .