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 IT 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-β 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.