RRC ID 39092
Author Natsume T, Tomita S, Iemura S, Kinto N, Yamaguchi A, Ueno N.
Title Interaction between soluble type I receptor for bone morphogenetic protein and bone morphogenetic protein-4.
Journal 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.
Volume 272(17)
Pages 11535-40
Published 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
Times Cited 69
Human and Animal Cells ST2(RCB0224)