| RRC ID |
39092
|
| 著者 |
Natsume T, Tomita S, Iemura S, Kinto N, Yamaguchi A, Ueno N.
|
| タイトル |
Interaction between soluble type I receptor for bone morphogenetic protein and bone morphogenetic protein-4.
|
| ジャーナル |
J Biol Chem
|
| Abstract |
Bone morphogenetic proteins (BMPs) are multifunctional proteins that comprise the largest subfamily of the transforming growth factor-beta. These proteins bind to types I and II serine/threonine kinase receptors. Ligand-induced heteromeric dimerization of these receptors is the key event in initiation of biological responses. We report here large-scale expression and purification of extracellular domain of the type I receptor for BMP-2/4, using a silkworm expression system. This soluble form of BMP receptor (sBMPR) was in monomer form in solution and bound to BMP-4 but not to activin or transforming growth factor-beta1. Surface plasmon resonance studies showed that kinetic parameters of sBMPR for BMP-4 consisted of a relatively rapid association rate constant (ka = 3.81 +/- 0.19 x 10(4) s-1 M-1) and an extremely slow dissociation rate constant (kd = 3.69 +/- 0.26 x 10(-4) s-1). From these two kinetic parameters, affinity was determined to be similar to that of the intact membrane-associated receptor expressed on COS cells. sBMPR inhibited the alkaline phosphatase activity in BMP responsive cell lines such as mouse osteoblastic cell MC3T3-E1 and bone marrow stromal cell ST2. These data indicate that the extracellular domain of type I receptor for BMP-2 and BMP-4 is sufficient for high-affinity binding to its ligands and should prove useful in understanding the role of BMP-2/4 in vivo, because a suitable high-affinity anti-BMP antibody has yet to be developed.
|
| 巻・号 |
272(17)
|
| ページ |
11535-40
|
| 公開日 |
1997-4-25
|
| DOI |
10.1074/jbc.272.17.11535
|
| PII |
S0021-9258(18)40671-0
|
| PMID |
9111068
|
| MeSH |
Amino Acid Sequence
Animals
Binding, Competitive
Biosensing Techniques
Bombyx / genetics
Bone Marrow / metabolism
Bone Marrow Cells
Bone Morphogenetic Protein 2
Bone Morphogenetic Protein 4
Bone Morphogenetic Protein Receptors, Type I
Bone Morphogenetic Proteins / antagonists & inhibitors
Bone Morphogenetic Proteins / metabolism*
Mice
Molecular Sequence Data
Peptide Fragments / genetics
Peptide Fragments / metabolism
Protein Binding
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / metabolism*
Receptors, Growth Factor / genetics
Receptors, Growth Factor / metabolism*
Recombinant Fusion Proteins / metabolism
Solubility
Stromal Cells / metabolism
Transforming Growth Factor beta*
|
| IF |
4.238
|
| 引用数 |
69
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
ST2(RCB0224) |
