OSTEOGENIC PROTEIN-1 BINDS TO ACTIVIN TYPE-II RECEPTORS AND INDUCES CERTAIN ACTIVIN-LIKE EFFECTS

被引:445
作者
YAMASHITA, H
TENDIJKE, P
HUYLEBROECK, D
SAMPATH, TK
ANDRIES, M
SMITH, JC
HELDIN, CH
MIYAZONO, K
机构
[1] LUDWIG INST CANC RES, S-75124 UPPSALA, SWEDEN
[2] CATHOLIC UNIV LEUVEN, CELGEN, MOLEC BIOL LAB, B-3000 LOUVAIN, BELGIUM
[3] CATHOLIC UNIV LEUVEN VIB, B-3000 LOUVAIN, BELGIUM
[4] CATHOLIC UNIV LEUVEN, CELL PHARMACOL LAB, B-3000 LOUVAIN, BELGIUM
[5] CREAT BIOMOLECULES INC, HOPKINTON, MA 01748 USA
[6] NATL INST MED RES, DEV BIOL LAB, LONDON NW7 1AA, ENGLAND
关键词
D O I
10.1083/jcb.130.1.217
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
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页码:217 / 226
页数:10
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