Identification of a Human Type II Receptor for Bone Morphogenetic Protein-4 That Forms Differential Heteromeric Complexes with Bone Morphogenetic Protein Type I Receptors (∗)

• Published in: The Journal of biological chemistry Vol. 270; no. 38; pp. 22522 - 22526
• Main Authors: Nohno, Tsutomu, Ishikawa, Tetsuya, Saito, Taiichi, Hosokawa, Keiichi, Noji, Sumihare, Wolsing, Dana Hance, Rosenbaum, Jan S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22.09.1995; American Society for Biochemistry and Molecular Biology
• Subjects: Base Sequence; Bone Morphogenetic Protein Receptors; Bone Morphogenetic Protein Receptors, Type II; Bone Morphogenetic Proteins; Cloning, Molecular; DNA Primers - chemistry; Gene Expression; Humans; Macromolecular Substances; Molecular Sequence Data; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Proteins - metabolism; Receptors, Cell Surface - metabolism; Receptors, Growth Factor; Recombinant Proteins - metabolism; RNA, Messenger - genetics
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.270.38.22522

Bone morphogenetic proteins (BMPs) comprise the largest subfamily of TGF-β-related ligands and are known to bind to type I and type II receptor serine/threonine kinases. Although several mammalian BMP type I receptors have been identified, the mammalian BMP type II receptors have remained elusive. We have isolated a cDNA encoding a novel transmembrane serine/threonine kinase from human skin fibroblasts which we demonstrate here to be a type II receptor that binds BMP-4. This receptor (BRK-3) is distantly related to other known type II receptors and is distinguished from them by an extremely long carboxyl-terminal sequence following the intracellular kinase domain. The BRK-3 gene is widely expressed in a variety of adult tissues. When expressed alone in COS cells, BRK-3 specifically binds BMP-4, but cross-linking of BMP-4 to BRK-3 is undetectable in the absence of either the BRK-1 or BRK-2 BMP type I receptors. Cotransfection of BRK-2 with BRK-3 greatly enhanced affinity labeling of BMP-4 to the type I receptor, in contrast to the affinity labeling pattern observed with the BRK-1 + BRK-3 heteromeric complex. Furthermore, a subpopulation of super-high affinity binding sites is formed in COS cells upon cotransfection only of BRK-2 + BRK-3, suggesting that the different heteromeric BMP receptor complexes have different signaling potential.