Characterization of the bone morphogenetic protein-2 as a neurotrophic factor - Induction of neuronal differentiation of PC12 cells in the absence of mitogen-activated protein kinase activation.
Characterization of the bone morphogenetic protein-2 as a neurotrophic factor - Induction of neuronal differentiation of PC12 cells in the absence of mitogen-activated protein kinase activation.
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DOI：
10.1074/jbc.271.29.17360
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发表时间：
1996-07-19
影响因子：
4.8
通讯作者：
Kohno, M
中科院分区：
文献类型：
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作者：
Iwasaki, S;Hattori, A;Kohno, M
大鼠嗜铬细胞瘤PC 12细胞显示表达骨形态发生蛋白（BMP）-2（1，300个受体/细胞，Kd = 31.3 pM）的单一类高亲和力结合位点。使用放射性标记的BMP-2的亲和交联证明存在表观分子量为170、155、105、90、80和70 kDa的六种组分。BMP-2诱导PC 12细胞的形态学变化，伴随着三种神经丝蛋白的表达。因此，BMP-2似乎是另一种神经营养因子，与神经生长因子或碱性成纤维细胞生长因子一样，刺激PC 12细胞的神经元分化。然而，与神经生长因子和碱性成纤维细胞生长因子不同，BMP-2不能诱导41和43 kDa促分裂原活化蛋白（MAP）激酶或MAP激酶/细胞外信号调节激酶激酶（MEK）的活化。BMP-2对PC 12细胞c-fos基因的表达无诱导作用。激活素A也能够诱导PC 12细胞的神经元分化，而不激活MAP激酶和MEK。这些发现显示了MAP激酶级联激活的需要与BMP-2和激活素A诱导PC 12细胞神经元分化的能力之间的明确分离。此外，这些结果表明，MAP激酶和MEK的激活不是PC 12细胞分化的绝对要求。
Rat pheochromocytoma PC12 cells are shown to express a single class of high affinity binding sites for bone morphogenetic protein (BMP)-2 (1,300 receptors/cell, K-d = 31.3 pM). Affinity cross-linking using radiolabeled BMP-2 demonstrated the presence of six components with apparent molecular masses of 170, 155, 105, 90, 80, and 70 kDa. BMP-2 induced morphological changes in PC12 cells with the concomitant expression of three neurofilament proteins. Thus, BMP-2 would appear to be another neurotrophic factor that, like nerve growth factor or basic fibroblast growth factor, stimulates the neuronal differentiation of PC12 cells. Unlike nerve growth factor and basic fibroblast growth factor, how ever, BMP-2 failed to induce the activation of either 41- and 43-kDa mitogen-activated protein (MAP) kinases or the MAP kinase/extracellular signal-regulated kinase kinase (MEK). Also, BMP-2 did not induce the expression of the c-fos gene in PC12 cells. Activin A was also capable of inducing the neuronal differentiation of PC12 cells without activating MAP kinases and MEK. These findings show a clear dissociation between the requirement for the activation of the MAP kinase cascade and the ability of BMP-2 and activin A to induce PC12 cell neuronal differentiation. In addition, these results suggest that the activation of MAP kinases and MEK is not an absolute requirement for PC12 cell differentiation.