Identification of type I receptors for osteogenic protein-1 and bone morphogenetic protein-4.
Bone morphogenetic proteins (BMPs) are multifunctional proteins, structurally related to transforming growth factor-beta (TGF-beta) and activin. TGF-beta 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-beta 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)-1 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.
ten Dijke
P
P
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
Yamashita
H
H
Sampath
T K
TK
Reddi
A H
AH
Estevez
M
M
Riddle
D L
DL
Ichijo
H
H
Heldin
C H
CH
Miyazono
K
K
D029404:Activin Receptors; D028341:Activins; D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D006801:Humans; D007265:Inhibins / Q000378:metabolism; D051379:Mice; D010802:Phylogeny; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000378:metabolism; D011994:Recombinant Proteins; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D016212:Transforming Growth Factor beta
C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D011506:Proteins; D017978:Receptors, Growth Factor; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D028341:Activins; D007265:Inhibins; D017346:Protein Serine-Threonine Kinases; D029404:Activin Receptors