Osteogenic protein-1 binds to activin type II receptors and induces certain activin-like effects.

Abstract

Abstract. Proteins in the TGF-[~ 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-[3 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 liB (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.

The BMP signaling and in vivo bone formation

“…Three type I receptors have been shown to bind BMP ligands, type IA and IB BMP receptors (BMPR-IA or ALK-3 and BMPR-IB or ALK-6) and type IA activin receptor (ActR-IA or ALK-2) (Koenig et al, 1994;ten Dijke et al, 1994;Macias-Silva et al, 1998). Three type II receptors for BMPs have also been identified and they are type II BMP receptor (BMPR-II) and type II and IIB activin receptors (ActR-II and ActR-IIB) (Yamashita et al, 1995;Nohno et al, 1995;Rosenzweig et al, 1995;Kawabata et al, 1995). Whereas BMPR-IA, IB, and II are specific to BMPs, ActR-IA, II, and IIB are also signaling receptors for activins.…”

Genetic interactions between activin type IIB receptor and Smad2 genes in asymmetrical patterning of the thoracic organs and the development of pancreas islets

“…In addition to activins, ActRIIA and ActRIIB have subsequently been shown to bind to other TGF-␤ family proteins, including BMP7, Nodal, GDF8/Myostatin, and GDF11/BP11 (Yamashita et al, 1995;Lee and McPherron, 2001;Yeo and Whitman, 2001;Oh et al, 2002). The precise roles of the different activin receptors and Smads are still unclear, but they may be ligand and/or cell-type specific.…”

Expression of transforming growth factor‐β superfamily receptors in rat eyes

“…zono et al 1994b). The type II receptor family has 5 members Rosenzweig et al 1995;Yamashita et al 1995Yamashita et al , 1996.…”