title: Specific interaction of type I receptors of the TGF-beta family with the immunophilin FKBP-12.
abstract: Transforming growth factor-beta (TGF-beta) 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-beta 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.
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital, Boston, MA 02114.
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.forename: P K
authors.initials: PK
authors.lastname: Donahoe
authors.forename: A S
authors.initials: AS
authors.lastname: Zervos
mesh_terms: D001667:Binding, Competitive; D002352:Carrier Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D017354:Point Mutation; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D016559:Tacrolimus / Q000378:metabolism; D022021:Tacrolimus Binding Proteins
chemical_list: D002352:Carrier Proteins; D006360:Heat-Shock Proteins; D018125:Receptors, Transforming Growth Factor beta; D011993:Recombinant Fusion Proteins; D017346:Protein Serine-Threonine Kinases; D022021:Tacrolimus Binding Proteins; D016559:Tacrolimus