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

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...

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Bibliographic Details
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
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.7518616