Specific Interaction of Type I Receptors of the TGF-β Family with the Immunophilin FKBP-12

• Published in: Science (American Association for the Advancement of Science) 1994-07, Vol.265 (5172), p.674-676
• Main Authors: Wang, Tongwen, Donahoe, Patricia K., Zervos, Antonis S.
• Format: Article
• Language: English
• Subjects: Amino acids; Analysis of the immune response. Humoral and cellular immunity; Antiserum; Binding sites; Binding, Competitive; Biological and medical sciences; Carrier Proteins - metabolism; Cell lines; Complementary DNA; DNA; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Heat-Shock Proteins - metabolism; Immunobiology; Ligands; Miscellaneous; Molecular interactions; Point Mutation; Precipitin Tests; Protein-Serine-Threonine Kinases - metabolism; Receptors; Receptors, Transforming Growth Factor beta - metabolism; Recombinant Fusion Proteins - metabolism; Regulatory factors and their cellular receptors; Saccharomyces cerevisiae; Tacrolimus - metabolism; Tacrolimus Binding Proteins; Yeasts
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.7518616

Transforming growth factor-β (TGF-β) family members bind to receptors that consist of heteromeric serine-threonine kinase subunits (type 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-β and with other type I receptors. Deletion, point mutation, and co-immunoprecipitation studies further demonstrated the specificity of the interaction. Excess FK506 competed with type I receptors for binding to FKBP-12, which suggests that these receptors share or overlap the macrolide binding site on FKBP-12, and therefore they may represent its natural ligand. The specific interaction between the type I receptors and FKBP-12 suggests that FKBP-12 may play a role in type I receptor-mediated signaling.