SPECIFIC INTERACTION OF TYPE-I RECEPTORS OF THE TGF-BETA FAMILY WITH THE IMMUNOPHILIN FKBP-12
SPECIFIC INTERACTION OF TYPE-I RECEPTORS OF THE TGF-BETA FAMILY WITH THE IMMUNOPHILIN FKBP-12
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DOI：
10.1126/science.7518616
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发表时间：
1994-07-29
期刊：
影响因子：
56.9
通讯作者：
ZERVOS, AS
中科院分区：
文献类型：
--
作者：
WANG, TW;DONAHOE, PK;ZERVOS, AS
转化生长因子- β (tgf - β)家族成员与由异聚丝氨酸-苏氨酸激酶亚基（I型和II型）组成的受体结合。在酵母基因筛选中，大环内酯类药物FK506和雷帕霉素的靶点——亲免疫蛋白FKBP-12与tgf - β的I型受体和其他I型受体相互作用。缺失、点突变和共免疫沉淀研究进一步证明了这种相互作用的特异性。过量的FK506与I型受体竞争与FKBP-12结合，这表明这些受体共享或重叠FKBP-12上的大环内酯结合位点，因此它们可能代表其天然配体。I型受体与FKBP-12之间的特异性相互作用表明FKBP-12可能在I型受体介导的信号传导中发挥作用。
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.