[Identification of receptors for bone morphogenetic proteins].
Bone morphogenetic protein (BMP)-7/osteogenic protein (OP)-1 and growth/differentiation factor (GDF)-5 are members of the BMP family. BMPs transduce their effects through binding to two different types of serine/threonine kinase receptors, type I and type II. Here we investigated the binding and signaling properties of BMP-7/OP-1 and GDF-5 through type I and type II receptors. BMP-7/OP-1 was found to bind Activin receptor-like kinase (ALK)-1 as well as ALK-3/BMPR-IA in ATDC5 cells. When ALK-1 or ALK-3/BMPR-IA was stably transfected into mink lung epithelial cells, ALK-1 and ALK-3/BMPR-IA mediated signals for BMP-7/OP-1 with heterogeneous signaling specificities. GDF-5 bound to ALK-6/BMPR-IB and BMP type II receptor (BMPR-II) but not to ALK-3/BMPR-IA in ROB-C26 cells. Analysis using COS-1 cells revealed that GDF-5 bound to ALK-6/BMPR-IB, but not to the other type I receptors when expressed alone. When COS-1 cells were transfected with type II receptor cDNAs, GDF-5 bound to Activin type II receptor (ActR-II) and type IIB receptors as well as BMPR-II but not to TGF-beta type II receptor. In the presence of type II receptors, GDF-5 bound to different sets of type I receptors, but the binding was most efficient to ALK-6/BMPR-IB compared to the other type I receptors. Moreover, GDF-5 transduced the signal efficiently by ALK-6/BMPR-IB in the presence of BMPR-II or ActR-II.
Nishitoh
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Second Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Tokyo Medical and Dental University.
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D002478:Cells, Cultured; D055428:Growth Differentiation Factor 5; D006133:Growth Substances / Q000502:physiology; D051379:Mice; D051381:Rats; D017978:Receptors, Growth Factor / Q000302:isolation & purification*; D015398:Signal Transduction / Q000502:physiology
D019485:Bone Morphogenetic Proteins; C525894:Gdf5 protein, mouse; D055428:Growth Differentiation Factor 5; D006133:Growth Substances; D017978:Receptors, Growth Factor