Osteogenic protein-1 binds to activin type II receptors and induces certain activin-like effects.
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.
Yamashita
H
H
Ludwig Institute for Cancer Research, Uppsala, Sweden.
ten Dijke
P
P
Huylebroeck
D
D
Sampath
T K
TK
Andries
M
M
Smith
J C
JC
Heldin
C H
CH
Miyazono
K
K
D029404:Activin Receptors; D028341:Activins; D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004627:Embryonic Induction / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D038681:Follistatin; D006023:Glycoproteins / Q000494:pharmacology; D006131:Growth Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007265:Inhibins / Q000494:pharmacology*; D008648:Mesoderm / Q000166:cytology; D008907:Mink; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism / Q000494:pharmacology*; D017978:Receptors, Growth Factor / Q000378:metabolism*; D011994:Recombinant Proteins; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D029867:Xenopus Proteins
C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D038681:Follistatin; D006023:Glycoproteins; D006131:Growth Inhibitors; D011506:Proteins; D017978:Receptors, Growth Factor; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D029867:Xenopus Proteins; C525822:bmp7.1 protein, Xenopus; D028341:Activins; D007265:Inhibins; D005640:Follicle Stimulating Hormone; D029404:Activin Receptors