SPECIFIC INTERACTION OF TYPE-I RECEPTORS OF THE TGF-BETA FAMILY WITH THE IMMUNOPHILIN FKBP-12

Transforming growth factor-beta (TGF-beta) family members bind to rece ptors that consist of heteromeric serine-threonine kinase subunits (ty pe I and type II). In a yeast genetic screen, the immunophilin FKBP-12 , a target of the macrolides FK506 and rapamycin, interacted with the type I receptor for TGF-beta and with other type I receptors. Deletion , point mutation, and co-immunoprecipitation studies further demonstra ted the specificity of the interaction. Excess FK506 competed with typ e I receptors for binding to FKBP-12, which suggests that these recept ors share or overlap the macrolide binding site on FKBP-12, and theref ore they may represent its natural ligand. The specific interaction be tween the type I receptors and FKBP-12 suggests that FKBP-12 may play a role in type I receptor-mediated signaling.