title: Characterization and cloning of a receptor for BMP-2 and BMP-4 from NIH 3T3 cells.
abstract: The bone morphogenetic proteins (BMPs) are a group of transforming growth factor beta (TGF-beta)-related factors whose only receptor identified to date is the product of the daf-4 gene from Caenorhabditis elegans. Mouse embryonic NIH 3T3 fibroblasts display high-affinity 125I-BMP-4 binding sites. Binding assays are not possible with the isoform 125I-BMP-2 unless the positively charged N-terminal sequence is removed to create a modified BMP-2, 125I-DR-BMP-2. Cross-competition experiments reveal that BMP-2 and BMP-4 interact with the same binding sites. Affinity cross-linking assays show that both BMPs interact with cell surface proteins corresponding in size to the type I (57- to 62-kDa) and type II (75- to 82-kDa) receptor components for TGF-beta and activin. Using a PCR approach, we have cloned a cDNA from NIH 3T3 cells which encodes a novel member of the transmembrane serine/threonine kinase family most closely resembling the cloned type I receptors for TGF-beta and activin. Transient expression of this receptor in COS-7 cells leads to an increase in specific 125I-BMP-4 binding and the appearance of a major affinity-labeled product of approximately 64 kDa that can be labeled by either tracer. This receptor has been named BRK-1 in recognition of its ability to bind BMP-2 and BMP-4 and its receptor kinase structure. Although BRK-1 does not require cotransfection of a type II receptor in order to bind ligand in COS cells, complex formation between BRK-1 and the BMP type II receptor DAF-4 can be demonstrated when the two receptors are coexpressed, affinity labeled, and immunoprecipitated with antibodies to either receptor subunit. We conclude that BRK-1 is a putative BMP type I receptor capable of interacting with a known type II receptor for BMPs.
authors.affiliation: Corporate Research Division, Miami Valley Laboratories, Procter & Gamble Company, Cincinnati, Ohio 45239-8707.
authors.forename: B B
authors.initials: BB
authors.lastname: Koenig
authors.forename: J S
authors.initials: JS
authors.lastname: Cook
authors.forename: D H
authors.initials: DH
authors.lastname: Wolsing
authors.forename: J
authors.initials: J
authors.lastname: Ting
authors.forename: J P
authors.initials: JP
authors.lastname: Tiesman
authors.forename: P E
authors.initials: PE
authors.lastname: Correa
authors.forename: C A
authors.initials: CA
authors.lastname: Olson
authors.forename: A L
authors.initials: AL
authors.lastname: Pecquet
authors.forename: F
authors.initials: F
authors.lastname: Ventura
authors.forename: R A
authors.initials: RA
authors.lastname: Grant
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D052005:Bone Morphogenetic Protein Receptors, Type I; D019485:Bone Morphogenetic Proteins; D029742:Caenorhabditis elegans Proteins; D003001:Cloning, Molecular; D015870:Gene Expression; D015801:Helminth Proteins / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000737:chemistry; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics*; D017978:Receptors, Growth Factor / Q000235:genetics*; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
chemical_list: D019485:Bone Morphogenetic Proteins; D029742:Caenorhabditis elegans Proteins; D015801:Helminth Proteins; D015345:Oligonucleotide Probes; D011506:Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; C083704:daf-4 protein, C elegans; D020794:Receptor Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; C498212:Bmpr1a protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I