Dedicator of cytokinesis (DOCK) proteins constitute a family of evolutionarily conserved guanine nucleotide exchange factors (GEFs) for the Rho family of GTPases. Although DOCK family proteins do not contain the Dbl homology domain typically found in other GEFs, they mediate the GTP-GDP exchange reaction through the DOCK homology region-2 (DHR-2) domain. In mammals, this family consists of 11 members, each of which has unique functions depending on the expression pattern and the substrate specificity. For example, DOCK2 is a Rac activator critical for migration and activation of leukocytes, whereas DOCK8 is a Cdc42-specific GEF that regulates interstitial migration of dendritic cells. Identification of DOCK2 and DOCK8 as causative genes for severe combined immunodeficiency syndromes in humans has highlighted their roles in immune surveillance. In addition, the recent discovery of a naturally occurring DOCK2-inhibitory metabolite has uncovered an unexpected mechanism of tissue-specific immune evasion. On the other hand, GEF-independent functions have been shown for DOCK8 in antigen-induced IL-31 production in helper T cells. This review summarizes multifaced functions of DOCK family proteins in the immune system.

中文翻译：

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DOCK家族蛋白：免疫监视机制的关键参与者。

胞质分裂（DOCK）蛋白的专用成分构成了GTPases Rho家族的进化保守的鸟嘌呤核苷酸交换因子（GEF）家族。尽管DOCK家族蛋白不包含通常在其他GEF中发现的Dbl同源结构域，但它们通过DOCK同源区域2（DHR-2）域介导了GTP-GDP交换反应。在哺乳动物中，该家族由11个成员组成，每个成员都具有独特的功能，具体取决于表达模式和底物特异性。例如，DOCK2是Rac激活剂，对白细胞的迁移和激活至关重要，而DOCK8是Cdc42特异性的GEF，它调节树突状细胞的间质迁移。将DOCK2和DOCK8鉴定为人类严重的综合免疫缺陷综合症的致病基因，突显了它们在免疫监视中的作用。另外，最近发现的天然存在的DOCK2抑制代谢物发现了组织特异性免疫逃逸的意外机制。另一方面，在辅助性T细胞中抗原诱导的IL-31产生中，DOCK8具有GEF依赖性功能。这篇综述总结了DOCK家族蛋白在免疫系统中的多方面功能。