Eph互作交换蛋白家族活性调控及调控异常相关疾病的研究进展

Research progress in activity regulation of Eph-interacting exchange protein family and diseases associated with abnormal activity regulation

Eph(erythropoietin-producing hepatocellular carcinoma)互作交换蛋白(Eph-interacting exchange protein,Ephexin)是鸟苷酸交换因子(guanine nucleotide exchange factors,GEFs)家族的最大亚家族Dbl(diffuse B-cell lymphoma)的亚群之一,主要在Ephrin配体与Eph受体介导的信号下激活,从而参与Rho蛋白的活性调节[1-2]。Rho蛋白是一类分子大小为20~30k D左右的Ras超家族成员之一,因其自身具有一段能将GTP水解成GDP的保守氨基酸序列,所以又叫Rho GTP酶。

Erythropoietin-producing hepatocellular carcinoma(Eph)-interacting exchange protein(Ephexin is a member of guanine nucleotide exchange factor(GEFs). The activity of Ephexins in the base state is inhibited. Ephexins are mainly activated and mediated by the combination of Ephrin ligands and Eph receptors,exhibiting their guanosine exchange activity,and are involved in regulating the activity of Rho proteins. There are 2 forms of Rho proteins in the cells,namely the inactive form that binds to guanosine diphosphate(Rho-GDP)and the active form that binds to guanosine triphosphate(Rho-GTP). The activated Rho-GTP protein binds and activates downstream effectors to trigger downstream signaling pathways. Members of the GEFs family,including Ephexins,regulate the conversion between these 2 forms of Rho proteins. The imbalance of guanosine exchange activity of Ephexins and abnormal regulation of Rho proteins may lead to the occurrence of cancer and many other diseases. This paper attempts to review the research progress in the structure and function of the Ephexin family,the molecular mechanism of Ephexin activation,the Rho protein activity regulation by Ephexins and the diseases associated with abnormal activity regulation.