Distribution and characterization of specific cellular binding proteins for bone morphogenetic protein-2.
Bone morphogenetic proteins (BMPs), which were originally identified by their novel ability to induce de novo cartilage and bone formation in vivo, are multifunctional proteins structurally related to transforming growth facto-beta s, activins, and inhibins. As a first step to elucidate the precise physiological function as well as the action mechanism of BMPs, we have examined the distribution of the specific cellular binding proteins for BMP-2 on a wide variety of cell types. A single class of high affinity-specific binding sites for BMP-2 were identified not only on osteoblastic cells but also on major types of non-hematopoietic cells in a rather ubiquitous fashion (1,200-60,000 receptors/cell, Kd = 35-230 pM); these cells included fibroblasts, keratinocytes, astrocytes, kidney epithelial cells, and tumor cells of bone, muscle, lung, liver, kidney, stomach, colon, prostate, and neuronal tissue. Other growth factors including transforming growth factor-beta 1, activin A, and inhibin A did not compete for the binding of 125I-labeled BMP-2 to the cells. Affinity cross-linking of radiolabeled BMP showed five components with apparent molecular masses of 170, 105, 90, 80, and 70 kDa common to all three fibroblast cell lines analyzed. On the other hand, no specific binding sites for BMP-2 were identified on vascular endothelial cells or on hematopoietic cells including RPMI 1788 and RPMI 8226 (B-lymphocyte lineage), MOLT-3 and MOLT-4 (T-lymphocyte lineage), HL-60 (myeloid lineage), and K-562 (erythroid lineage). These results suggest that major types of cells other than hematopoietic cells and vascular endothelial cells may be potential targets for BMP-2 action.
Iwasaki
S
S
Department of Biology, Gifu Pharmaceutical University, Japan.
Tsuruoka
N
N
Hattori
A
A
Sato
M
M
Tsujimoto
M
M
Kohno
M
M
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism; D012831:Bombyx; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D002461:Cell Line, Transformed; D004730:Endothelium, Vascular / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes; D007700:Kinetics; D051379:Mice; D009928:Organ Specificity; D010006:Osteoblasts / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D014407:Tumor Cells, Cultured
D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D006133:Growth Substances; D007457:Iodine Radioisotopes; D011506:Proteins; D011994:Recombinant Proteins