Bone morphogenetic protein-3 family members and their biological functions
Bone morphogenetic protein-3 family members and their biological functions
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DOI：
10.2741/1355
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发表时间：
2004-05-01
影响因子：
3.1
通讯作者：
Nishimatsu, S
中科院分区：
文献类型：
--
作者：
Hino, J;Kangawa, K;Nishimatsu, S
骨形态发生蛋白-3和骨形态发生蛋白-3b(BMP-3和BMP-3b)共同代表着BMP家族中一个独特的亚类。BMP-3b在成熟区(配体结构域)与BMP-3有82%的氨基酸同源性，但在亲区(PRO-结构域)的氨基酸同源性仅为37%。在成骨细胞中，BMP-3和3b对BMP-2具有相似的拮抗活性，但它们的调节方式不同。在胚胎发育过程中，BMP-3和3b具有不同的背化活性。BMP-3b以自主的方式触发二次头部形成，而BMP-3诱导异常的尾部形成。功能丧失分析表明，xBMP-3b和头部诱导剂Cerberus的协同活性是非洲爪哇胚胎头部形成所必需的。在分子水平上，BMP-3b既拮抗结节样蛋白(Xnr1和derriere)又拮抗腹壁BMP(BMP-2和ADMP)，而BMP-3仅拮抗腹壁BMP。此外，BMP-3b，而不是BMP-3，与Xnr1的单体形式有关，Xnr1是一种结节状蛋白。BMP-3和3b的这些分子特征是由于它们各自不同的前启动区。这些发现表明，BMP-3和BMP-3b前体区域的加工和组装在各种发育过程和器官发生中是重要的。
Bone morphogenetic protein-3 and 3b (BMP-3 and BMP-3b) together represent a unique subgroup of the BMP family. BMP-3b shares 82% amino acid identity with BMP-3 in the mature region (ligand domain), but only 37% in the pro-region (pro-domain). In osteoblasts, BMP-3 and 3b have similar antagonistic activity against BMP-2, but they are differentially regulated. In developing embryos, BMP-3 and 3b have different dorsalizing activities. BMP-3b triggers secondary head formation in an autonomous manner, whereas BMP-3 induces aberrant tail formation. Loss-of-function analysis demonstrates that coordinated activity of xBMP-3b and cerberus, a head inducer, are required for head formation in Xenopus embryos. At the molecular level, BMP-3b antagonizes both nodal-like proteins (Xnr1 and derriere) and ventralizing BMPs (BMP-2 and ADMP), whereas BMP-3 only antagonizes ventralizing BMPs. Moreover, BMP-3b, but not BMP-3, associates with the monomeric form of Xnr1, a nodal-like protein. These molecular features of BMP-3 and 3b are due to their distinct pro-regions. These findings suggest that the processing of precursor regions and assembly of BMP-3 and 3b are important in various developmental processes and organogenesis.