State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, 220 Handan Road, Shanghai, 200433, People's Republic of China.
Mol Cell Biochem. 2012 Jan;359(1-2):115-23. doi: 10.1007/s11010-011-1005-0. Epub 2011 Jul 30.
Members of the transforming growth factor-β (TGF-β) superfamily have significant roles in the regulation of a wide variety of physiological processes. In our present work, phylogenetic tree analysis showed that human GDF3 (Growth and differentiation factor 3) and human GDF1 formed a subgroup of closely related molecules. Through quantitative real-time PCR analysis in different human tissues, GDF1 and GDF3 expression level had a big difference in brain. GDF3 could activate downstream signaling through associating with ALK7 (Activin receptor-like kinase 7) in a Cripto-dependent fashion. A CHO cell line stably transfected with the encoding sequence of GDF3, named CHO-GDF3, was established. Western blotting analysis demonstrated that GDF3 protein could be secreted into the medium from CHO cells and immunofluorescence experiment showed that GDF3 was mainly distributed in cytoplasm of the stable cell line, the primary hippocampal neurons, and brain tissues. Furthermore, the conditioned medium from CHO-GDF3 could reduce PC12 cell growth and induce cell differentiation. All these findings bring new insights into the functional study of GDF3.
转化生长因子-β（TGF-β）超家族成员在广泛的生理过程调节中具有重要作用。在我们目前的工作中，系统进化树分析表明，人类 GDF3（生长分化因子 3）和人类 GDF1 形成了一个密切相关的分子亚群。通过对不同人体组织的实时定量 PCR 分析，GDF1 和 GDF3 的表达水平在大脑中有很大差异。GDF3 可以通过与 Cripto 依赖性的 ALK7（激活素受体样激酶 7）结合来激活下游信号。通过转染编码序列，建立了稳定转染 GDF3 的 CHO 细胞系，命名为 CHO-GDF3。Western blot 分析表明，GDF3 蛋白可以从 CHO 细胞分泌到培养基中，免疫荧光实验表明，GDF3 主要分布在稳定细胞系、原代海马神经元和脑组织的细胞质中。此外，来自 CHO-GDF3 的条件培养基可以减少 PC12 细胞的生长并诱导细胞分化。所有这些发现为 GDF3 的功能研究提供了新的见解。
