CDB15:0000129 BMP4 — BMPR1B
Experimentally validated in Mixed species, Mouse; Orthology-inferred in Human, Mouse, Rat, Frog, Zebrafish, Chicken, Macaque, Pig, Dog, Cow, Chimp, Horse, Marmoset, Sheep
Title
Journal:; Year Published:
Abstract
Synergistic effects of different bone morphogenetic protein type I receptors on alkaline phosphatase induction.
Journal of cell science, 2001; PubMed, Mus Musculus Bmp4 — Mus Musculus Bmpr1b
ABSTRACT: Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta superfamily, which regulate the differentiation of osteoprogenitor cells. Here we show that among members of the BMP family, BMP-4 and growth/differentiation factor 5 (GDF-5) induce osteoblast differentiation through the activation of three receptor-regulated Smads (i.e. Smad1, Smad5 and Smad8). By contrast, BMP-6 and BMP-7 induce alkaline phosphatase activity through Smad1 and Smad5, but not through Smad8. Consistent with these findings, BMP-4 induced phosphorylation and nuclear translocation of Smad1, Smad5 and Smad8, but BMP-6 activated only Smad1 and Smad5. BMP-4 and GDF-5 are known to bind to activin receptor-like kinase 3 (ALK-3) and/or ALK-6 (also termed BMP type IA and type IB receptors, respectively), whereas BMP-6 and BMP-7 preferentially bind to ALK-2. Compared with the effects induced by only one of the type I receptors, the combination of constitutively active forms of ALK-2 and ALK-3 (or ALK-6) more strongly induced alkaline phosphatase activity in C2C12 cells. Moreover, addition of BMP-4 and BMP-6 to C2C12 cells resulted in higher alkaline phosphatase activity than that of only one of these BMPs. The combination of ALK-2 and ALK-3 also induced higher transcriptional activity than either receptor alone. Thus, ALK-2 and ALK-3 (or ALK-6) might synergistically induce osteoblast differentiation of C2C12 cells, possibly through efficient activation of downstream signaling pathways.
A mammalian serine/threonine kinase receptor specifically binds BMP-2 and BMP-4.
Biochemical and biophysical research communications, 1994; PubMed, Homo sapiens BMP4 — Rattus norvegicus Bmpr1b
ABSTRACT: Bone morphogenetic proteins (BMPs) are a class of related growth and differentiation factors within the TGF-beta superfamily of proteins which are known to induce cartilage and bone formation in adult animals and to be involved in many inductive events throughout embryonic development. Here we describe the molecular cloning and characterization of a mammalian receptor, CFK-43a, which specifically binds BMP-2 and BMP-4. This molecule is a member of the serine/threonine kinase receptor family which includes receptors for other TGF-beta superfamily members. CFK-43a binds other BMP family members with lower affinity, but does not bind TGF-beta. During embryogenesis, in situ hybridization analysis indicates that CFK-43a mRNA is localized in developing skeletal tissues in a complementary fashion to the transcripts for its ligands.
Identification of type I receptors for osteogenic protein-1 and bone morphogenetic protein-4.
The Journal of biological chemistry, 1994; PubMed, Homo sapiens BMP4 — Mus Musculus Bmpr1b
ABSTRACT: Bone morphogenetic proteins (BMPs) are multifunctional proteins, structurally related to transforming growth factor-beta (TGF-beta) and activin. TGF-beta and activin exert their effects by forming heteromeric complexes of type I and type II serine/threonine kinase receptors. We have previously identified a series of type I serine/threonine kinase receptors, termed activin receptor-like kinase (ALK)-1 to -6. ALK-5 is a TGF-beta type I receptor, whereas ALK-2 and ALK-4 are activin type I receptors. Here we investigated the binding of proteins in the BMP family to ALKs. In transfected COS cells, the binding of osteogenic protein (OP)-1 and BMP-4 to certain ALKs was observed in the absence of type II receptors, and their binding was increased after co-transfection of a BMP type II receptor from Caenorhabditis elegans, DAF-4. OP-1 bound to ALK-2 and ALK-6 efficiently, and to ALK-3 less efficiently, whereas BMP-4 bound to ALK-3 and ALK-6 efficiently. Similarly, OP-1 bound to ALK-2, ALK-3, and/or ALK-6 in various nontransfected cell lines, although the binding profiles were different between different cell types. BMP-4 bound to ALK-3 in MC3T3-E1 osteoblasts and human foreskin fibroblasts. These results suggest that ALK-3 and ALK-6 are type I receptors for OP-1 and BMP-4; in addition, ALK-2 is a type I receptor shared by activin and OP-1, but not by BMP-4.