Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore, Singapore.
Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore.
Front Immunol. 2020 Sep 29;11:566192. doi: 10.3389/fimmu.2020.566192. eCollection 2020.
Downstream of kinase (Dok) 3 is a member of the Dok family of adaptor proteins known to regulate signaling pathways downstream of various immunoreceptors. As Dok-3 lacks intrinsic catalytic activity, it functions primarily as a molecular scaffold to facilitate the nucleation of protein complexes in a regulated manner and hence, achieve specificity in directing signaling cascades. Since its discovery, considerable progress has been made toward defining the role of Dok-3 in limiting B cell-receptor signaling. Nonetheless, Dok-3 has since been implicated in the signaling of Toll-like and C-type lectin receptors. Emerging data further demonstrate that Dok-3 can act both as an activator and inhibitor, in lymphoid and non-lymphoid cell types, suggesting Dok-3 involvement in a plethora of signal transduction pathways. In this review, we will focus on the structure and expression profile of Dok-3 and highlight its role during signal transduction in B cells, innate cells as well as in bone and lung tissues.
下游激酶 (Dok) 3 是衔接蛋白 Dok 家族的一个成员,已知其可调节各种免疫受体下游的信号通路。由于 Dok-3 缺乏内在的催化活性,因此它主要作为分子支架,以调节方式促进蛋白质复合物的成核,从而在指导信号级联反应方面实现特异性。自发现以来,人们在确定 Dok-3 在限制 B 细胞受体信号方面的作用方面取得了相当大的进展。尽管如此,Dok-3 此后还被牵连到 Toll 样和 C 型凝集素受体的信号转导中。新出现的数据进一步表明,Dok-3 可以在淋巴样和非淋巴样细胞类型中作为激活剂和抑制剂发挥作用,这表明 Dok-3 参与了多种信号转导途径。在这篇综述中,我们将重点介绍 Dok-3 的结构和表达谱,并强调其在 B 细胞、先天细胞以及骨骼和肺部组织中的信号转导中的作用。