Cunningham N S, Jenkins N A, Gilbert D J, Copeland N G, Reddi A H, Lee S J
Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Growth Factors. 1995;12(2):99-109. doi: 10.3109/08977199509028956.
We have identified a new member of the transforming growth factor-beta (TGF-beta) superfamily, growth/differentiation factor-10 (GDF-10), which is highly related to bone morphogenetic protein-3 (BMP-3). The nucleotide sequence of GDF-10 encodes a predicted protein of 476 amino acids with a molecular weight of approximately 52,000. The GDF-10 polypeptide contains a potential signal sequence for secretion, a putative RXXR proteolytic processing site, and a carboxy-terminal domain with considerable homology to other known members of the TGF-beta superfamily. In the mature carboxy-terminal domain GDF-10 is more homologous to BMP-3 (83% amino acid sequence identity) than to any other previously identified TGF-beta family member. GDF-10 also shows significant homology to BMP-3 (approximately 30% amino acid sequence identity) in the pro- region of the molecule. Based on these sequence comparisons, GDF-10 and BMP-3 define a new subgroup within the larger TGF-beta superfamily. By Northern analysis, GDF-10 mRNA was detected primarily in murine uterus, adipose tissue, and brain and to a lesser extent in liver and spleen. In addition, GDF-10 mRNA was present in both neonatal and adult bone samples, with higher levels being detected in calvaria than in long bone. These results suggest that GDF10 may play multiple roles in regulating cell differentiation events, including those involved in skeletal morphogenesis. Gdf10 was mapped to the proximal region of mouse chromosome 14 close to a region known to contain a spontaneous recessive mutation that is associated with a craniofacial defect.
我们鉴定出了转化生长因子-β（TGF-β）超家族的一个新成员——生长/分化因子-10（GDF-10），它与骨形态发生蛋白-3（BMP-3）高度相关。GDF-10的核苷酸序列编码一个预测的含476个氨基酸的蛋白质，分子量约为52,000。GDF-10多肽包含一个潜在的分泌信号序列、一个假定的RXXR蛋白水解加工位点以及一个与TGF-β超家族其他已知成员具有相当同源性的羧基末端结构域。在成熟的羧基末端结构域中，GDF-10与BMP-3的同源性（氨基酸序列同一性为83%）高于与任何其他先前鉴定的TGF-β家族成员的同源性。GDF-10在分子的前区与BMP-3也显示出显著的同源性（氨基酸序列同一性约为30%）。基于这些序列比较，GDF-10和BMP-3在更大的TGF-β超家族中定义了一个新的亚组。通过Northern分析，GDF-10 mRNA主要在小鼠子宫、脂肪组织和脑中检测到，在肝脏和脾脏中检测到的量较少。此外，GDF-10 mRNA在新生和成年骨样本中均有存在，在颅骨中检测到的水平高于长骨。这些结果表明，GDF10可能在调节细胞分化事件中发挥多种作用，包括那些参与骨骼形态发生的事件。Gdf10被定位到小鼠染色体14的近端区域，靠近一个已知包含与颅面缺陷相关的自发隐性突变的区域。
