Identification of type I receptors for osteogenic protein-1 and bone morphogenetic protein-4

Peter Ten Dijke, Hidetoshi Yamashita, T. Kuber Sampath, A Hari Reddi, Miguel Estevez, Donald L. Riddle, Hidenori Ichijo, Carl Henrik Heldin, Kohei Miyazono

Research output: Contribution to journalArticle

629 Scopus citations

Abstract

Bone morphogenetic proteins (BMPs) are multifunctional proteins, structurally related to transforming growth factor-β (TGF-β) and activin. TGF-β and activin exert their effects by forming heteromeric complexes of type I and type II serine/threonine kinase receptors. We have previously identified a series of type I serine/threonine kinase receptors, termed activin receptor-like kinase (ALK)-1 to -6. ALK-5 is a TGF-β type I receptor, whereas ALK-2 and ALK-4 are activin type I receptors. Here we investigated the binding of proteins in the BMP family to ALKs. In transfected COS cells, the binding of osteogenic protein (OP)-I and BMP-4 to certain ALKs was observed in the absence of type II receptors, and their binding was increased after co-transfection of a BMP type II receptor from Caenorhabditis elegans, DAF-4. OP-1 bound to ALK-2 and ALK-6 efficiently, and to ALK-3 less efficiently, whereas BMP-4 bound to ALK-3 and ALK-6 efficiently. Similarly, OP-1 bound to ALK-2, ALK-3, and/or ALK-6 in various nontransfected cell lines, although the binding profiles were different between different cell types. BMP-4 bound to ALK-3 in MC3T3-E1 osteoblasts and human foreskin fibroblasts. These results suggest that ALK-3 and ALK-6 are type I receptors for OP-1 and BMP-4; in addition, ALK-2 is a type I receptor shared by activin and OP-1, but not by BMP-4.

Original languageEnglish (US)
Pages (from-to)16985-16988
Number of pages4
JournalJournal of Biological Chemistry
Volume269
Issue number25
StatePublished - Jun 24 1994
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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    Ten Dijke, P., Yamashita, H., Sampath, T. K., Reddi, A. H., Estevez, M., Riddle, D. L., Ichijo, H., Heldin, C. H., & Miyazono, K. (1994). Identification of type I receptors for osteogenic protein-1 and bone morphogenetic protein-4. Journal of Biological Chemistry, 269(25), 16985-16988.