Regulation of neural cell adhesion molecule and L1 by the transforming growth factor-beta superfamily. Selective effects of the bone morphogenetic proteins.
The transforming growth factor-beta (TGF-beta) superfamily plays a role in embryogenesis and regeneration. We have reported that osteogenic protein-1 (OP-1) promotes cell aggregation and induces the expression of the neural cell adhesion molecules N-CAM and L1 in proliferating neuroblastoma x glioma hybrid NG108-15 cells (Perides, G., Safran, R. M., Rueger, D. C., and Charness, M. E. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 10326-10330; Perides, G., Hu, G., Rueger, D. C., and Charness, M. E. (1993) J. Biol. Chem. 268, 25197-25205). Here we show that the structurally homologous bone morphogenetic proteins (BMP) BMP-2 and BMP-4 are 10-50-fold more potent in these actions than the subfamily comprising BMP-5, BMP-6, and OP-1 (BMP-7). In contrast, members of the TGF-beta subfamily, activin-A, inhibin-A, and 29 additional growth factors and cytokines did not induce N-CAM. The addition of serum to cells growing in serum-free medium caused a concentration-dependent increase in N-CAM and L1 expression; however, serum did not potentiate the induction of N-CAM and L1 by 40 ng/ml OP-1. These findings suggest the presence in NG108-15 cells of a BMP-2/BMP-4 receptor that discriminates subtle differences in structure among homologous members of the TGF-beta superfamily. An endogenous ligand for this receptor may be present in serum.
Perides
G
G
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115.
Safran
R M
RM
Downing
L A
LA
Charness
M E
ME
D000818:Animals; D001769:Blood; D019485:Bone Morphogenetic Proteins; D002417:Cattle; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis*; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D039841:Leukocyte L1 Antigen Complex; D005810:Multigene Family; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured
D019485:Bone Morphogenetic Proteins; D015816:Cell Adhesion Molecules, Neuronal; D006133:Growth Substances; D039841:Leukocyte L1 Antigen Complex; D011506:Proteins; D016212:Transforming Growth Factor beta