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 rol e 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 ne uroblastoma 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 B MP-4 are 10-50-fold more potent in these actions than the subfamily co mprising BMP-5, BMP-6, and OP-1 (BMP-7). In contrast, members of the T GF-beta subfamily, activin-A, inhibin-A, and 29 additional growth fact ors and cytokines did not induce N-CAM. The addition of serum to cella growing in serum-free medium caused a concentration-dependent increas e in N-CAM and Li expression; however, serum did not potentiate the in duction of N-CAM and L1 by 40 ng/ml OP-1. These findings suggest the p resence in NG108-15 cells of a BMP-2/BMP-4 receptor that discriminates subtle differences in structure among homologous members of the TGF-b eta superfamily. An endogenous ligand for this receptor may be present in serum.