Osteogenic protein-1 binds to activin type II receptors and induces certain activin-like effects.
Osteogenic protein-1 binds to activin type II receptors and induces certain activin-like effects.
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DOI：
10.1083/jcb.130.1.217
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发表时间：
1995-07
期刊：
影响因子：
--
通讯作者：
Miyazono K
中科院分区：
文献类型：
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作者：
Yamashita H;ten Dijke P;Huylebroeck D;Sampath TK;Andries M;Smith JC;Heldin CH;Miyazono K
TGF-β超家族中的蛋白质通过与I型和II型丝氨酸/苏氨酸激酶受体结合来发挥其作用。成骨蛋白-1（OP-1，也称为骨形态发生蛋白-7或BMP-7），属于BMP亚家族的TGF-β超家族的成员，被发现在存在II型激活素受体（ActR-II）和IIB型激活素受体（ActR-IIB）的情况下结合I型激活素受体（ActR-I）以及IA型BMP受体（BMPR-IA）和IB型BMP受体（BMPR-IB）。OP-1与ActR-II的结合亲和力比激活素A低2 - 3倍。在OP-1与ActR-I和ActR-II的复合物或BMPR-IB和ActR-II的复合物结合后，转导转录激活信号。这些结果表明ActR-II可以作为OP-1以及激活素的功能性II型受体。对OP-1观察到激活素的一些已知生物学效应，包括生长抑制和红细胞分化诱导。与激活素相比，OP-1被证明是爪蟾胚胎中中胚层的不良诱导剂。此外，发现激活素的抑制剂卵泡抑素抑制OP-1的作用，如果以10倍过量添加。然而，对于OP-1，未观察到激活素的某些作用，如诱导大鼠垂体细胞中的促卵泡激素分泌。OP-1与激活素具有重叠的结合特异性，并且共享激活素的某些但非全部功能效应。因此，OP-1在体内的作用可能比迄今为止认识到的更广泛。
Proteins in the TGF-beta superfamily transduce their effects through binding to type I and type II serine/threonine kinase receptors. Osteogenic protein-1 (OP-1, also known as bone morphogenetic protein-7 or BMP-7), a member of the TGF-beta superfamily which belongs to the BMP subfamily, was found to bind activin receptor type I (ActR-I), and BMP receptors type IA (BMPR-IA) and type IB (BMPR-IB) in the presence of activin receptors type II (ActR-II) and type IIB (ActR-IIB). The binding affinity of OP-1 to ActR-II was two- to threefold lower than that of activin A. A transcriptional activation signal was transduced after binding of OP-1 to the complex of ActR-I and ActR-II, or that of BMPR-IB and ActR-II. These results indicate that ActR-II can act as a functional type II receptor for OP-1, as well as for activins. Some of the known biological effects of activin were observed for OP-1, including growth inhibition and erythroid differentiation induction. Compared to activin, OP-1 was shown to be a poor inducer of mesoderm in Xenopus embryos. Moreover, follistatin, an inhibitor of activins, was found to inhibit the effects of OP-1, if added at a 10-fold excess. However, certain effects of activin, like induction of follicle stimulating hormone secretion in rat pituitary cells were not observed for OP-1. OP-1 has overlapping binding specificities with activins, and shares certain but not all of the functional effects of activins. Thus, OP-1 may have broader effects in vivo than hitherto recognized.