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

T. Nohno, T. Ishikawa, T. Saito, K. Hosokawa, S. Noji, D. H. Wolsing, J. S. Rosenbaum

Research output: Contribution to journalArticle

196 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
DOIs
Publication statusPublished - Jan 1 1995
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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