双亮氨酸拉链激酶DLK对JNK信号通路的调控作用及机制

Regulation of the JNK signaling pathway by dual leucine zipper kinase DLK

c-Jun氨基末端激酶(c-Jun NH2-ternimal kinase,JNK)属于进化上相当保守的促分裂原活化蛋白激酶(Mitogen-activated protein kinase,MAPK)超家族。大量的研究揭示,JNK在细胞增殖、分化、迁移、凋亡和形态建成中起着关键作用,并与多种人类疾病的发生与发展密切相关。双亮氨酸拉链激酶(DLK)在结构上属于MLK(Mixed lineage kinase)家族,功能上则是MAPKKK(MAP kinase kinase kinase)中一员,可通过MAPKK(MAP kinase kinase)对JNK的活性进行调节,从而参与细胞凋亡、迁移、分化等一系列重要细胞反应。文章结合DLK与JNK的研究历史与最新进展,就DLK-JNK通讯所参与的细胞凋亡、迁移及分化等活动做一简要综述。

The C-Jun NH2-terminal kinase（JNK） belongs to the evolutionarily conserved sub-group of mitogen-activated protein（MAP） kinases family.Many studies have shown that JNK pathway plays physiological roles in cell proliferation,differentiation,migration and apoptosis,and its deregulation has been associated with developmental defects and various human diseases.Dual leucine zipper kinase（DLK） is a member of the mixed-lineage kinases that performs important cellu-lar functions as a MAP triple kinase（MAPKKK） in regulating the JNK signaling pathway.In this paper,we described the DLK protein structures,physiological roles,and their functional interactions with JNK signaling,as well as the molecular mechanisms underlying their involvement in various human diseases.