Identification of a human type II receptor for bone morphogenetic protein-4 that forms differential heteromeric complexes with bone morphogenetic protein type I receptors

Tsutomu Nohno, Tetsuya Ishikawa, Taiichi Saito, Keiichi Hosokawa, Sumihare Noji, Dana Hance Wolsing, Jan S. Rosenbaum

Research output: Contribution to journalArticle

192 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)22522-22526
Number of pages5
JournalJournal of Biological Chemistry
Volume270
Issue number38
Publication statusPublished - Sep 22 1995
Externally publishedYes

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Type I Bone Morphogenetic Protein Receptors
Bone Morphogenetic Protein 4
Forensic Anthropology
Protein-Serine-Threonine Kinases
COS Cells
Labeling
Type II Bone Morphogenetic Protein Receptors
Bone Morphogenetic Protein Receptors
Bone Morphogenetic Proteins
Fibroblasts
Skin
Phosphotransferases
Complementary DNA
Genes
Binding Sites
Tissue
Ligands

ASJC Scopus subject areas

  • Biochemistry

Cite this

Identification of a human type II receptor for bone morphogenetic protein-4 that forms differential heteromeric complexes with bone morphogenetic protein type I receptors. / Nohno, Tsutomu; Ishikawa, Tetsuya; Saito, Taiichi; Hosokawa, Keiichi; Noji, Sumihare; Wolsing, Dana Hance; Rosenbaum, Jan S.

In: Journal of Biological Chemistry, Vol. 270, No. 38, 22.09.1995, p. 22522-22526.

Research output: Contribution to journalArticle

Nohno, Tsutomu ; Ishikawa, Tetsuya ; Saito, Taiichi ; Hosokawa, Keiichi ; Noji, Sumihare ; Wolsing, Dana Hance ; Rosenbaum, Jan S. / Identification of a human type II receptor for bone morphogenetic protein-4 that forms differential heteromeric complexes with bone morphogenetic protein type I receptors. In: Journal of Biological Chemistry. 1995 ; Vol. 270, No. 38. pp. 22522-22526.
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