Perides G, Safran R M, Downing L A, Charness M E
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115.
J Biol Chem. 1994 Jan 7;269(1):765-70.
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.
转化生长因子-β（TGF-β）超家族在胚胎发生和再生过程中发挥作用。我们曾报道，成骨蛋白-1（OP-1）可促进细胞聚集，并诱导增殖的神经母细胞瘤x胶质瘤杂交NG108-15细胞中神经细胞黏附分子N-CAM和L1的表达（佩里德斯，G.，萨夫兰，R.M.，鲁格，D.C.，和查尼斯，M.E.（1992年）《美国国家科学院院刊》89，10326 - 10330；佩里德斯，G.，胡，G.，鲁格，D.C.，和查尼斯，M.E.（1993年）《生物化学杂志》268，25197 - 25205）。在此我们表明，结构同源的骨形态发生蛋白（BMP）BMP-2和BMP-4在这些作用中的效力比由BMP-5、BMP-6和OP-1（BMP-7）组成的亚家族高10 - 50倍。相比之下，TGF-β亚家族的成员、激活素-A、抑制素-A以及另外29种生长因子和细胞因子均未诱导N-CAM的表达。向无血清培养基中生长的细胞添加血清会导致N-CAM和L1表达呈浓度依赖性增加；然而，血清并不能增强40 ng/ml OP-1对N-CAM和L1的诱导作用。这些发现表明，NG108-15细胞中存在一种BMP-2/BMP-4受体，该受体能够区分TGF-β超家族同源成员之间细微的结构差异。血清中可能存在该受体的内源性配体。
